|
|
Next Article 
Blood, Vol. 90 No. 8 (October 15), 1997:
pp. 2863-2892
REVIEW ARTICLE
Recent Advances in Flow Cytometry: Application to the Diagnosis of Hematologic Malignancy
By
C. Darrell Jennings and
Kenneth A. Foon
From the Departments of Pathology and Laboratory Medicine and Internal Medicine, Division of Hematology and Oncology, University of Kentucky, College of Medicine, and the Lucille Parker Markey Cancer Center, Lexington, KY.
 |
INTRODUCTION |
OVER A DECADE HAS passed since "Immunologic Classification of Leukemia and Lymphoma" by Foon and Todd was published in Blood.1 Over this decade, flow cytometry has evolved from a promising new technology to an indispensable tool in the diagnosis of hematologic malignancies. Many new antibodies, improved gating strategies, and routine use of multiparameter techniques have dramatically improved the diagnostic utility of flow cytometry.
This review will focus on the use of flow cytometry in the routine clinicopathologic approach to the diagnosis of leukemias and lymphomas, emphasizing the relevant literature of the past 10 years. Some of the recent advances in flow cytometric monitoring of disease and treatment are shown in the last section. We will review the use of flow cytometry in the diagnosis of major disorders highlighting the prognostically important subgroups defined either morphologically or genetically. The discussion will focus not only on the use of flow cytometry in the differential diagnosis of a particular disorder, but also correlate immunophenotypic, molecular, and cytogenetic data in the delineation of biologically important subgroups. It is our intent that this review support a combined modality approach to the daily practice of hematology-oncology and hematopathology. A working knowledge of the basics of flow cytometry is assumed; thus, technical aspects of instrumentation, normal distribution of surface antigens, and methodologies are not included, but have recently been reviewed.2-13
| |
ACUTE LEUKEMIA |
Flow cytometric analysis of acute leukemia is interpretive, combining the patterns and intensity of antigen expression to reach a definitive diagnosis.1-13 Gating is critical to isolate the abnormal cells because the leukemic phenotype should be determined on as pure a population as possible. Most leukemias involve the analysis of bone marrow. Standard forward and side scatter gating is not optimal for separating bone marrow cells because of the overlap between monocytes, blasts, myelocytes, promyelocytes, and metamyelocytes. As bone marrow cells mature, they express increasing CD45. Thus, when CD45 is combined with side scatter, which separates lineages based on cytoplasmic complexity, the bone marrow sample is readily separated into its cellular constituents.14 Infiltration of marrow by immature cells or blasts is more easily recognized on a CD45 versus side-scatter plot than on traditional forward side-scatter gating (Fig 1).
View larger version (41K):
[in this window]
[in a new window]
| Fig 1.
Analysis of normal and leukemic bone marrow by CD45-side scatter analysis. (A) Normal marrow illustrating several normal populations. (B) Lymphoblasts as seen in ALL. (C) Treated CML illustrating transition to acute phase with increased myeloblasts and a reactive increase in erythroid precursors. (D) Low-grade lymphoproliferative disorder illustrated by CLL. These patterns are representative and are not specifically diagnostic in the absence of other data.
|
|
Acute myeloid leukemia (AML).
AML is traditionally subclassified by morphology and cytochemistry according to the French-American-British (FAB) criteria as modified by the National Cancer Institute-Sponsored Workshop that incorporates immunophenotypic data.15 Although the major role of flow cytometry is to provide immunophenotypic data, cellular morphology can be examined by both forward-side scatter16,17 and CD45-side scatter analysis.14 We will summarize each of the major subtypes of AML below incorporating the morphologic, immunologic, and cytogenetic (MIC) approach.18,19
The ability of flow cytometry to identify myeloid versus lymphoid differentiation approaches 98%.20,21 However, the prognostic value of immunophenotypic data is controversial.21-26 Studies that failed to find prognostic value for immunophenotyping generally looked at the correlation of outcome with individual antigens and did not find clinically useful associations, although the utility of flow cytometry in defining myeloid differentiation was confirmed.21-24 Studies that found correlation with specific phenotypes were generally single institution results. Three of the four studies showing no correlation were in children,21-23 in whom there is some evidence that the t(8; 21) may not carry the same good prognosis as in adults.27 Additionally, differences in reagents, gating and staining techniques, and thresholds for positivity may account for discrepancy.
Correlating clinical outcome with specific antigens rather than the total phenotype is probably not useful. Lymphoid antigen expression in AML is associated with both poor, t(9; 22) and 11q23 rearrangements, and favorable, t(8; 21), t(15; 17), and inv(16), prognostic genetic alterations.21,28,29 For example, CD19 expression may be associated with either t(9; 22) or t(8; 21).29 It is not simply the expression of CD19 in AML that is important but the context in which it occurs. Additionally, unusual antigen combinations, although of limited prognostic value, can be useful in the detection of minimal residual disease29 (see last section).
It is our impression that genetic phenotypes carry the most important prognostic information. Unfortunately, there are few entirely consistent relationships between morphology, immunophenotype, and specific genetic alterations.30,31 There exist trends that are discussed below. However, in general, for any given genetic phenotype, there are patients with more than one possible FAB subtype or immunophenotype. We have chosen to place genotypic information in the FAB section in which the particular genotype is most commonly observed. Thus, we will discuss the immunophenotype of AML in the context of morphology and correlate with genetic phenotype where appropriate, similar to the MIC approach to diagnosis.21,28,32,33 AML is summarized in Table 1 based on the most common phenotypes with inclusion of possible genetic associations.
M0.
M0 blasts have low forward and side scatter and typically merge with the lymphoblast region on CD45-side scatter plots. By definition, the blasts are cytochemically negative but express at least one myeloid specific marker such as CD13, CD33, or CD11b.34 Detection of the cytoplasmic enzyme myeloperoxidase (MPO) by monoclonal antibody appears more sensitive than CD13 and CD33 combined.35 Blasts are generally negative for lymphoid markers, but may express CD7 or CD4.21,35 M0 blasts are almost always positive for HLA-DR and CD34.35,36 Several investigators have shown an association between CD7 as well as CD34 expression in AML and a worse prognosis.26,37-45 These antigens may relate to expression of drug resistance phenotypes discussed in the last section. M0 is associated with a high incidence of cytogenetic abnormalities, most of which are complex but frequently involve chromosomes 5 and 7.35,36,46
M1.
The flow appearance of M1 is similar to M0 and probably not separable. There may be slightly more side-scatter reflecting the cytochemically positive granules, but this is not definitive in a single case. M1 blasts are usually CD13+, CD33+, and HLA-DR+, but may not express as much CD34 as M0. There may be partial CD15 expression and less commonly CD4.35
M2.
The major difference between M2 and M1 is the presence of maturation and a reduced percentage of blasts. Typically, there is a spectrum of cells with varying degrees of light scatter. CD45-side scatter can show a continuum of cells from the myeloblast region to the maturing myeloid cell regions. CD34 is less prominent and CD15 is more prominent than in M1. Most cases are HLA-DR+. CD13 is sometimes expressed more brightly than CD33. CD45-side scatter may be useful in determining the percentage of blasts.
Expression of CD19 and less often CD56 in the context of M2 is associated with the presence of t(8; 21),29,47-50 a favorable prognostic marker in adults.51,52 Rare patients with M2 morphology and t(8; 21) are CD13-, CD33-, and CD14- but MPO+.53
M3.
The hypergranular form shows abundant side scatter despite reduced CD45 compared with mature cells and absence or reduction of HLA-DR in most cases. The microgranular variant is not as obvious morphologically or by light scatter, but does show a similar phenotype. CD34 is less prominent than is seen in M2.35 CD33 and weak CD13 are generally present.54 CD2 may be seen in M335 and the microgranular variant (M3v).55 CD2 in an HLA-DR- AML is correlated with M3 and t(15; 17).29,48,56 Recognition of a possible M3 morphology or flow phenotype is important in that it probably demands genetic analysis. There is a correlation between M3 and rearrangements of the retinoic acid receptor- (RAR-) locus.57 However, some of these may be cytogenetically silent and require molecular methods for detection.58 The presence of RAR- rearrangements predicts response to ALL-trans retinoic acid (ATRA), a major therapeutic advance.59 Thus, patients with M3 or suggestive flow phenotype and negative cytogenetics should be tested by molecular methods for RAR- rearrangements. In addition, some patients with a hypergranular morphology and HLA-DR- phenotype will have a variant translocation such as t(11; 17) and less favorable response to ATRA and chemotherapy.60 Molecular testing is also made necessary because of another newly described entity, myeloid/natural killer cell acute leukemia, with morphology and immunophenotype also similar to M3, but without RAR- rearrangements. This disorder is HLA-DR-, CD33+, CD13 weak, CD34 variable, and CD56+ with morphology similar to M3v.61 It is seen in an older population, tends to be aggressive, and does not respond to ATRA.
ATRA therapy is not entirely benign. A complication is the sometimes fatal retinoic acid syndrome. This syndrome has been correlated with the expression of CD13 in the pretreatment leukemia population.62-64
M4 and M5.
These two categories are similar phenotypically although M4 is more often CD34+ than M5.35 M4 and M5 cells have more forward and side scatter than M0 and M1. By CD45-side scatter, the maturing cells merge into the monocytic region. Maturation into the myeloid region as well should occur with M4, but this is not entirely reproducible. Important phenotypic features are the presence of CD13, CD33, HLA-DR, CD14, and CD15.35 CD33 may be brighter than CD13. The combination of CD33 positivity with negative CD13 and CD34 is highly correlated with an M5 phenotype, but occurs in only a minority of patients.29 CD56 may be seen in some cases of M5.29 Subtle clues to monocytic differentiation may be weak CD7 or CD4 expression35 and in our experience nonspecific binding of  and  light chains and IgG but not IgD and to a lesser extent IgM. Some cases of M5b may be entirely in the monocyte region on CD45-side scatter. The presence of CD2 is correlated with an important subtype M4Eo that is associated with abnormalities of chromosome 16 and a better prognosis.65-69
M6.
M6 is rare and not well characterized. HLA-DR, CD34, and possibly CD13 or CD33 are usually present. CD45-side scatter may show a prominent erythroid component. Antibodies to glycophorin may demonstrate erythroid differentiation.70,71
M7.
Acute megakaryoblastic leukemia (M7) accounts for less than 1% of AML4 and is diagnosed when greater than 30% of the nonerythroid cells are megakaryoblasts. The megakaryoblastic nature of the blasts must be confirmed by ultrastructural demonstration of platelet peroxidase or by immunophenotyping. Micromegakaryocytes are not counted as blasts but raise the possibility of M7.15 Immunophenotyping is important because neither morphologic nor routine cytochemical features are pathognomonic and ultrastructural techniques are difficult.72 Megakaryoblasts are typically identified by the expression of CD61 (GpIIIa) and/or CD41 (GpIIb-IIIa).72-74 However, caution must be exercised as false-positive reactions may occur due to platelet adherence to leukemia blasts.72 In one study of more than 1,000 cases of AML, 38% were positive for CD41. Comparison to cytospin immunoflourescence in 37 cases showed that 85% of the apparent expression of CD41 was due to adherent platelets. Therefore, confirmation of flow cytometric results by cytospin immunofluorescence is probably necessary in cases of M7.72 An interesting approach to reduce binding of activated platelets is two-color flow cytometry for GPIIb/IIIa and CD34 in the presence of EDTA.75
Extramedullary leukemia.
The increasing use of immunophenotyping in fine needle aspiration of solitary tissue masses makes it likely that extramedullary leukemia will be encountered. In a recent review of extramedullary leukemia, 46% of cases were initially misdiagnosed.76 Two-thirds of patients receiving chemotherapy for a solitary primary site of extramedullary leukemia never developed AML, whereas 97% not treated initially with chemotherapy progressed to AML, emphasizing the importance of systemic therapy.76 A second review also emphasized the importance of prompt chemotherapy over radiation or surgery.77 An association between chloromas and t(8; 21) may exist.78 Accurate initial diagnosis of extramedullary leukemia is important and is another potential use of flow cytometric immunophenotyping.
Acute lymphoblastic leukemia (ALL).
ALL is the most frequent malignancy of children, comprising 25% of all cancers.79 In adults, ALL accounts for 20% of acute leukemia, affecting 2 persons per 100,000 annually.80 ALL is a heterogeneous disease with biologically and clinically distinct subsets.81-83 Immunophenotyping plays a central role in the determination of clinically relevant subsets. Although intensive therapy may blur some prognostic distinctions, consideration of toxicity/efficacy ratios and the persistence of definable high-risk groups requires the continued use of immunophenotyping in the diagnosis and classification of ALL.80-83
ALL is initially divided into B and T lineages with the B lineage further subdivided into B-cell, pre-B-cell, and early B-precursor types. In children, the B-precursor phenotype has been the most favorable with the notable exception of CD10- disease in infants.83,84 In adults, overall results are less favorable due in part to the increased representation of t(9; 22) in the B-precursor group.80 However, new treatment regimens have resulted in improved outcome for adults, particularly with T-ALL.80-82
We divide ALL into B-precursor ALL, CD10+ or CD10-, pre-B ALL, B-ALL, and T-ALL. Infantile ALL is usually recognized by its unique phenotype described below. We concur with a recent review that classification should be based on the pattern of reactivity to a panel of lineage associated antibodies, rather than any specific reagent.83 ALL may also be classified on the basis of DNA content, which is readily measured by flow cytometry.85 The two most important subgroups are the hyperdiploid cases with a better prognosis86 and the hypodiploid cases with a poor prognosis.87 Table 2 summarizes the lymphoid leukemias based on the most common phenotypes.
B-precursor ALL.
B-precursor ALL accounts for 65% to 70% of ALL in infants and children, 55% to 60% in adolescents, and 50% in adults. In children, more than 90% are CD10+, whereas less than 50% are positive in infants.83
The blasts are typically small with minimal forward and side scatter. These cells are typically L1 or L2 by the FAB criteria. Some cases may have very low or absent CD45 merging them with the erythroid cluster on CD45-side scatter. The phenotype is positive for TdT, HLA-DR, and CD19. We recognize two subgroups, namely CD10+ and CD10-, because of the more favorable prognosis of the former.88 Most cases are also CD24+ and CD34+. CD20 increases with maturity. B-precursor ALL is by definition surface membrane Ig (SIg) negative. CD10 negativity may be most important in infants89 in whom it may signal a biologically distinct subset. Infants around 1 year of age with ALL that is CD19+, CD10-, and express aberrant CD15 are likely to have a translocation involving 11q23 and a poor prognosis.90-92
Among patients with a B-precursor phenotype, several specific genetic alterations dramatically affect prognosis. The first of these is t(9; 22), which creates the BCR-ABL fusion gene that encodes a chimeric tyrosine kinase with markedly increased activity resulting in cell proliferation and leukemogenesis.81,93-95 The BCR-ABL fusion gene is present in 30% of adult ALL patients96 and 3% to 5% of pediatric cases.97 In both groups it is associated with a dismal prognosis.81,83,96,98,99 One study of 197 patients yielded a 3-year survival of 62% for BCR-ABL and t(9; 22)-negative patients versus 16% for those positive with either method.99 There is a significantly lower detection rate by classical cytogenetics compared with molecular methods (23% v 30%).96
Translocations involving 11q23 occur in about 60% of ALL in infants, 2% in children, and 3% to 6% in adults.81 These translocations most often result in rearrangement of the MLL gene and are associated with a very poor prognosis.91,92,100,101 The phenotype is CD10-, B-precursor, or pre-B with aberrant myeloid antigens, particularly CD15.81,90,100,101 Molecular analysis will detect a significant number of 11q23 rearrangements not seen by classical cytogenetics.101
Both the t(9; 22) and 11q23 translocations are associated with expression of myeloid-associated antigens.102-104 Although the presence of myeloid associated antigens in ALL is not clearly associated with an adverse prognosis per se,105 their presence in an infant or adult with ALL and normal cytogenetics probably warrants molecular analysis for 11q23 translocations or BCR-ABL as appropriate.
An important recent finding is the t(12; 21)(p21; q22), which creates a chimeric product TEL/AML1 previously thought to be rare (<0.05%) in ALL based on classical cytogenetics.106 Altered activity of AML1, which is part of the AML1/CBF transcription factor complex also altered in t(8; 21) and inv(16), is thought to be the essential feature.106 Use of molecular methods has shown the presence of the TEL/AML1 fusion mRNA in approximately 20% to 25% of childhood ALL, making it the most frequent genetic abnormality in pediatric ALL.107-109 The t(12; 21) defines a subgroup of ALL patients that are between 1 and 10 years of age with nonhyperdiploid DNA content, a B-lineage phenotype with HLA-DR, CD19, and CD10, and an excellent prognosis.107-109 It is probably important to include molecular analysis for the t(12; 21) in the work-up of pediatric ALL, particularly when the above-mentioned features are present.
Hematogones.
Hematogones are an important normal finding in the marrow and peripheral blood of both children and adults after chemotherapy for acute leukemia.110-113 Increased numbers of CD19+, CD10+ B precursors are seen in a variety of settings, but they are most disturbing after treatment for B-precursor ALL. Unless there are specific tumor-associated markers, one must be very careful in the interpretation of CD19+, CD10+ cells after chemotherapy or bone marrow transplantation. The percentage of such cells can occasionally approach levels suggesting acute leukemia. An observation is the tendency of hematogones to represent a spectrum of maturation; however, a recent paper describes a quantitative flow method for distinguishing hematogones from residual ALL.114
Pre-B-cell ALL.
Pre-B ALL recapitulates a later stage of B-lineage than the early B-precursor. This phenotype occurs in about 25% of children with ALL,83,115,116 but has not been well studied in adults.81 Cells are typically CD19+, CD24+, HLA-DR+, cytoplasmic CD22+, and CD10+. TdT is variable as is CD20. CD34 is generally negative. The defining characteristic is the presence of cytoplasmic µ heavy chain. The pre-B phenotype has traditionally been associated with a worse outcome than the early B-precursor phenotype.116,117 This adverse outcome appears to be more closely linked to the presence of t(1; 19).118,119 The t(1; 19) is present in approximately 5% of childhood early B-lineage ALL102 and 25% of pre-B ALL81 and results in the creation of an E2A-PBX1 fusion product. It is associated with a specific phenotype: CD19+, CD10+, and CD9+, variable expression of CD20, and CD34-.120 The immunophenotype appears 100% sensitive for t(1; 19) with generation of the E2A-PBX1 fusion product. Only 8% of ALL exhibits this phenotype, which has a predictive value of 50%. Recognition of this phenotype is important in stimulating molecular analysis in cytogenetically silent or ambiguous cases. The most useful single marker in this study was absence of CD34 in the context of a CD19+, CD10+ ALL. The absence of CD34 is also an independent poor prognostic marker in general in B-lineage ALL.121
B-ALL.
Mature B-cell ALL represents 2% to 5% of all ALL81,83 and is equivalent to Burkitt's lymphoma in leukemic phase. Virtually all of these patients have translocations involving C-MYC at 8q24 and either the heavy chain locus at 14q32 or light chains at 2p11 or 22q11.81 Although children now fair better than before, with cure rates of 60% to 78% when treated intensively,83 this remains a poor prognostic phenotype for adults.80,82,99,105 Recent results with intensive therapy are encouraging, but illustrate the importance of correct recognition of this phenotype to select the most appropriate therapy.80,82,122,123
The B-cell ALL cells have more forward and side scatter than B-precursor cells and may merge with the lymphocyte and monocyte regions on CD45 side scatter plots. They are L3 by the FAB criteria. The phenotype shows B-lineage antigens CD19, CD20, CD22, and CD24 with bright clonal SIg most often IgM. Many cases are CD10+, but the mature antigens and SIg distinguish it from earlier B-lineage ALL.
Rare patients have a mature B-cell acute leukemia without FAB-L3 morphology. These patients tend to have extensive bone marrow involvement at presentation and an aggressive course.124 Some patients have FAB-L1 morphology and coexistent t(1; 19) and t(14; 18).125,126
T-ALL.
A T-cell phenotype is present in 25% of adult81 and 15% of childhood83 ALL. Many of these cases will have significant forward and side scatter and may be in either the lymphoblast, myeloblast, or monocytic regions on CD45-side scatter. Most cases show a thymic phenotype. The most common phenotype seems to be a late cortical with CD1, CD2, CD5, CD7, and dual CD4/CD8 with minimal surface CD3. TdT is frequently positive. Next most common is an early cortical phenotype with CD2, CD5, and CD7 and strong TdT. A medullary phenotype, CD2, CD5, CD7, with segregated CD4 or CD8 and CD3 is less common and also less likely to express TdT. A pre-T-cell phenotype is CD7 and cytoplasmic CD3 positive without other T-cell antigens and may have a worse outcome,127 although this is controversial.105 A hallmark of all T-cell neoplasms is the tendency to drop specific normal T-cell antigens or display aberrant combinations.48
Adults with a T-cell phenotype tend to have a better outcome.99,105 In children, the T-cell phenotype is associated with older age, male gender, mediastinal mass, and central nervous system involvement.83 These children do less well than those with pre-B or early B-precursor phenotypes.83,84,128 Prognostically important subsets are not well defined,83 but CD10- cases appear to do worse.83,89,129
Recent reports describe patients with lymphoblastic lymphoma, eosinophilia, and myeloid hyperplasia or AML.130,131 These cases appear to be associated with t(8; 13)(p11; q11).130
Acute undifferentiated leukemia.
With the advent of flow cytometry, only about 1% of acute leukemias remain unclassified.132 The use of cytoplasmic markers in addition to surface markers may allow assignment of lineage to some of these cases.133 Typical undifferentiated acute leukemias are HLA-DR+ and CD34+ with no lineage-specific antigens. Although there is evidence that lineage-specific markers present on blasts may reflect the phenotype of the leukemia colony-forming cell,134 the relationship of the clonogenic cell or cells to their more differentiated progeny remains extremely complex.135-137
Biphenotypic leukemia.
The widespread application of flow cytometric immunophenotyping to leukemia has led to the recognition of many cases that do not fit uniformly into standard myeloid or lymphoid lineages. Initially, most of these were termed biphenotypic or mixed lineage leukemias. In some series, the incidence approached 50%. In a review of 746 cases of acute leukemia,47 7% fulfilled strict criteria for biphenotypic leukemia. In another study, cases of AML with isolated expression of TdT, B-cell, or T-cell antigens did not correlate with Ig or TCR gene rearrangements. In contrast, expression of two or more lymphoid antigens did correlate with Ig or TCR rearrangements.138 True bilineage phenotype is most consistently encountered in patients with t(9; 22) or rearrangements of the MLL gene at (11q23).28,138-140 An interesting group of patients mentioned above with t(8; 13) have lymphoblastic lymphoma and myeloid hyperplasia or AML. We strongly support the use of strict, uniform diagnostic criteria. Many cases of apparent biphenotypic acute leukemia represent aberrant patterns associated with specific genetic alterations, as described in this review. The most common problems leading to overdiagnosis of biphenotypic leukemia are failure to exclude nonleukemia cells from the analysis, overinterpretation of weak nonspecific binding, and failure to recognize the lack of lineage specificity of several antibodies. Recent advances in understanding the biologic function of the molecules carrying individual CD epitopes has elucidated their lack of lineage fidelity.141 For example, CD10 and CD13 are membrane-associated enzymes with common structural and regulatory features.141 The most important lineage-specific antigens are cytoplasmic CD22, CD3, and MPO for B, T, and myeloid lines, respectively.
| |
CHRONIC MYELOGENOUS LEUKEMIA (CML) |
CML is a myeloproliferative disorder of the hematopoietic stem cell involving myeloid, erythroid, megakaryocytic, B lymphocytes, sometimes T lymphocytes, but not marrow fibroblasts.142,143 Similarities exist with other myeloproliferative diseases, including polycythemia vera, essential thrombocytosis, and myeloid metaplasia. Because of the significant cellular differentiation during the chronic phase, flow cytometry is of little use, reflecting only a normal marrow phenotype except for myeloid predominance by CD45-side scatter. The diagnosis of CML is confirmed by the presence of the Philadelphia chromosome (Ph1 ), which represents the reciprocal translocation of the distal genetic material of chromosomes 9 and 22, t(9; 22)(q34; q11).144,145 This translocation transposes the C-ABL proto-oncogenes from chromosome 9 to a new position on chromosome 22 in proximity to the breakpoint cluster region (BCR ), forming a new hybrid BCR-ABL oncogene. The BCR-ABL produces an abnormal 8.5-kb RNA that encodes for a 210-kD (p210) fusion protein that changes normal hematopoietic cells into CML cells.146 This product may be a target for in situ polymerase chain reaction (PCR) using labeled primers detected by flow cytometry. Such molecular flow cytometry techniques are under investigation and would extend the analytic power of flow cytometry into the molecular arena.147
CML initially presents in the chronic or benign phase with an indolent course heralded by elevated white blood cell counts including more primitive myeloid cells normally found only in the bone marrow as well as increased basophils and eosinophils. Early in the course of the disease, elevated platelets are typically found and often an elevated red blood cell count is also found. The blood counts in the chronic phase can be controlled with hydroxyurea, busulfan, or interferon-.148 Survival advantages are reported for patients with major cytogenetic responses to interferon-.149 Allogeneic bone marrow transplantation for curative intent is recommended for patients who meet the criteria for transplantation.150 With conventional therapy, chronic-phase CML eventually progresses to an accelerated phase, lasting approximately 1 year or less, followed by the acute or blastic phase.148 Flow cytometry is most useful determining the phenotype of the acute phase, which has therapeutic implications.
The acute or blastic phase of CML usually presents as myeloid, but occasionally may be lymphoid. Myeloid acute phase may present in multiple morphologic forms, including undifferentiated. Lymphoid acute-phase cells have the typical morphology and surface markers of CD10+ B-precursor ALL.151 A T-cell ALL is rarely diagnosed.152-154 Patients with lymphoid acute phase have a high response to standard ALL therapy such as vincristine and prednisone with or without an anthracycline.151 Responses typically last 6 to 12 months, but relapse is inevitable and all patients eventually succumb to disease. This is in marked contrast to myeloid acute phase, which is typically highly refractory to standard AML therapy. Median survival of lymphoid acute phase is 9 months versus 3 months for nonlymphoid acute phase151; thus, it is critical to differentiate the type of acute phase to design appropriate therapy.
Experimental studies of peripheral blood and bone marrow CML cells that may not yet be useful in standard practice are nonetheless interesting and have important implications for future trials. Investigators have shown that cells expressing CD34 antigen, but lacking the HLA-DR antigen in long-term bone marrow cultures are Ph1 negative as well as negative for BCR-ABL mRNA, whereas HLA-DR+ long-term culture cells are Ph1 positive and positive for BCR-ABL mRNA.155 This suggests that a Ph1 benign stem cell population could be selected for autologous bone marrow transplantation. Other investigators have shown that long-term marrow culture selects clonogenic cells that are Ph1 negative156 that have been used for autologous bone marrow transplantation.157
| |
CHRONIC LYMPHOCYTIC AND PROLYMPHOCYTIC LEUKEMIAS |
Chronic lymphocytic leukemia (CLL) is the most common adult leukemia in Western Europe and North American.158-162 The predominant cell is a small lymphocyte that may be slightly larger than normal lymphocytes. The lymph node counterpart is small cell lymphocytic lymphoma (SLL). A variable proportion of prolymphocytes is frequently present and occasional cases show lymphoplasmacytoid features or other histologic variations.160,163,164 Abnormal morphology is more common in patients with trisomy 12.160,162,165 The immunophenotype typically shows dim expression of SIgM and SIgD with clonal light chain restriction; B-cell-associated antigens CD19, CD20, CD43, and CD79a are coexpressed with CD5 in almost all cases.158-164 CD23 expression helps distinguish CLL from mantle cell lymphoma, which is CD23-.166 CD10 and CD22 are negative, whereas CD11c and CD25 are often expressed, but tend to be weak.158-164,167 CD20 is also characteristically weak in CLL.168
Although CLL is generally indolent, there is a wide range of survival.158-164 Patients with chromosomal abnormalities tend to have a poorer prognosis. The most common abnormalities are trisomy 12 and abnormalities of 14q, 13q, and 11q. No single consistent abnormality is present and immunophenotype does not uniformly predict specific genetic changes,158-163,165 although recent reports suggest that trisomy 12 is correlated with higher intensity SIg and CD20, absent CD23, and higher frequency of FMC7.169,170
B-prolymphocytic leukemia (B-PLL) is typically a more aggressive disease than CLL.160,164 Flow cytometry is very useful in distinguishing CLL from B-PLL.159,160,171 B-PLL cells show stronger Sig and are usually CD5- and CD22+.159,160,164,171 One potential problem is differentiating the prolymphocytic transformation of CLL from de novo PLL.159,160,164,171,172 In some patients with CLL and disease progression, the percentage of PLL cells increases. If this percentage exceeds 30%, it is called prolymphocytic transformation of CLL. The immunophenotype of the transformed prolymphocytes differs from that seen in de novo PLL. In prolymphocytic transformation, the prolymphocytes express CD5 and dim SIg, similar to the CLL cells.159,160,173 It remains controversial160 whether the prolymphocytic transformation of CLL portends a poorer prognosis. It is our experience and the experience of others159 that this transformation parallels the natural disease progression and does not necessarily independently represent a poor prognosis.
Patients with mantle cell lymphomas (described below) have a median survival of less than 5 years, but may be difficult to distinguish from CLL morphologically. Similar to CLL, they are CD5+ B cells.174 However, the SIg is brighter than is seen in CLL, and the cells lack CD23. In one study of 540 unselected consecutive cases of CLL, independent variables for reduced survival were age, clinical stage, weak CD23, and bright SIgM among the CD5+ cases.175 Some of the CD23 weak, SIgM bright cases likely represent mantle cell lymphoma. In the same study, CD5- cases, which had borderline significant low survival compared with CD5+ cases were typically CD23- with strong SIgM and splenomegaly.175 Some of these cases may have been de novo B-PLL. Some have proposed that CD5- CLL represents an intermediate between classical CLL and de novo B-PLL.176 There appear to be differences in VH gene usage between CD5+ and CD5- CLL cases.177-179 Another study correlated the CD5- negative cases with myelomonocytic antigens.179
Another low-grade lymphoproliferative disorder that overlaps CLL is peripheral blood involvement by follicular center cell (FCC) lymphomas (described below). These cells typically have bright SIg and are CD5-, CD10+, CD23+, with B-lineage phenotype. Generally, these cells are morphologically distinct, but may overlap the above disorders. Our current practice and that of others161,180 is to question cases of CLL that are CD5-. Cases with FMC7 and CD22 or inappropriately bright SIg and CD20 may represent prolymphocytic leukemia, mantle cell, or FCC lymphoma181 or they may be a subgroup of CLL (trisomy 12) at greater risk for a more aggressive course. Immunophenotyping combined with morphology provide a mechanism for definitive diagnosis of patients with low-grade B-cell lymphoproliferative disorders.182 The B-cell lymphoproliferative disorders are summarized in Table 3.
A consistent finding in CLL is high-level expression of the BCL-2 gene despite its infrequent translocation.183,184 This may be a future target for flow cytometric analysis. Approximately 3% to 5% of CLL cases transform to a diffuse large-cell lymphoma (Richter transformation). Unfortunately, there is no consistent or predictive genetic change172,185 or phenotype.
We and others have used multiparameter flow cytometry for the detection of minimal residual disease after treatment186,187 (Fig 2). Figure 2 shows the dilution of CLL cells in normal blood and their recovery by three-color analysis to approximately 1%.
View larger version (32K):
[in this window]
[in a new window]
| Fig 2.
The use of three-color analysis to detect minimal disease in CLL. CLL cells have been diluted to 1% in normal peripheral blood. (A) Plot of CD5 versus CD20 is used to gate dual-positive cells with weak CD20 in the left sided histogram. These gated cells are then plotted on the right-sided histograms for both CD20 versus and CD20 versus , showing clonality with a12:1 ratio of to for the dual CD5, CD20+ cells.
|
|
| |
LYMPHOMA |
Flow cytometry has assumed an important role in the diagnosis of lymphoma.188,189 Samples are frequently directly processed lymph nodes or fine needle aspirates (FNA) of lymph nodes or other tissues, blood, and bone marrow.188,190-192 Immunophenotyping is a powerful adjunct to cytomorphology in the diagnosis of lymphoma by FNA191,192 and may spare patients expensive surgical procedures. The ability to identify specific lymphomas depends on recognition of a pattern of antigen expression, as detailed below. The presence of an aberrant pattern may allow detection of small numbers of neoplastic cells admixed with normal cells (Fig 2). This multiparametric capability of flow cytometry is uniquely valuable.189 Additionally, many lymphomas and leukemias exhibit characteristic alteration of antigen density such as decreased CD20 in CLL/SLL and increased CD20 in hairy cell leukemia; similarly, low-intensity SIg in SLL versus high-intensity SIg in FCC. Thus, the quantitative nature of flow cytometry is very important. Flow cytometry also allows the quantitation of DNA content of individual cells, permitting the determination of cell cycle characteristics of a population such as the S-phase or G2-M fractions. Alterations in chromosome number producing an aneuploid population may also be detected. The S-phase fraction may have prognostic significance for certain lymphomas.193,194 Flow cytometry may also be used to assess the proliferative fraction as reflected by expression of the Ki-67 epitope.195 The Ki-67-associated proliferation antigen was recently shown to identify a subgroup of non-Hodgkin's lymphomas with very poor prognosis in a large cooperative trial.196
| |
MANTLE CELL LYMPHOMAS (MCL) |
MCL combines the previously recognized entities intermediate lymphocytic lymphoma (ILL), lymphocytic lymphoma of intermediate differentiation (IDL), centrocytic lymphoma, and mantle zone lymphoma (MZL).174 MCL represents 2% to 8% of lymphomas.197 Most patients are older, with a male predominance, and present with generalized lymphadenopathy, hepatomegaly, and frequent, sometimes massive, involvement of spleen and bone marrow. Peripheral blood involvement and a leukemic presentation is not unusual, but cytopenias are uncommon.164,197-201 Extranodal disease occurs, particularly in the gastrointestinal tract, in which it may take the form of multiple lymphomatous polyposis.202
This is a clonal B-cell neoplasm, more common than , IgM intermediate, IgD weak or negative, with CD19, 20, 22, and 43. Most cases are CD5+ and CD23-. CD10 is usually negative, but has been reported sometimes coexpressed with CD5.203 The presence of CD5, lack of CD23, and Ig pattern help distinguish MCL from FCC. The intensity of Ig light chain and IgM, weaker IgD, lack of CD23, and brighter CD20 distinguish MCL from CLL/SLL. The phenotype is transitional between CLL and FCC. Hairy cell leukemia can be eliminated by the lack of CD11c, CD103, and usually CD25.164,174,197-202,204,205
Immunophenotype combined with morphology and clinical picture will usually distinguish MCL from other lymphocytic neoplasms. This is necessary because most of these neoplasms are low-grade lesions, whereas clearly MCL is not. Median survival is less than 5 years without a plateau, and a blastic variant is more aggressive. Therapy has not been promising.164,174,197,201,204-208
MCL is associated with a specific cytogenetic alteration t(11; 14)(q13; q32), which results in rearrangement and deregulation of the BCL-1/PRAD-1 proto-oncogene leading to overexpression of the cyclin D1 protein.209-213 This translocation is present in 50% to 60% of MCL209,212-214 and may also be detected by a PCR amplification, although the sensitivity may be less than cytogenetics.205,214 When patients were selected for expression of CD5 and BCL-1 rearrangements, a very homogeneous group with adenopathy, high stage, bone marrow involvement, intense CD20, no CD10, and poor prognosis resulted.215 The overexpression of PRAD-1/cyclin D1 in MCL, which is independent of BCL-1 rearrangements presently detectable, appears to be a highly sensitive and specific molecular marker of MCL.216 Overexpression of the cyclin D1 protein product has also been studied at the protein level by immunohistochemistry and correlates well with Northern blot analysis.214 Cyclin D1 detection by multiparameter flow cytometry after cell permeabilization may offer an excellent diagnostic technique that may be superior to molecular methods.
Although overexpression of cyclin D1 is a sensitive and specific marker for MCL, levels do not correlate with clinical behavior.216 There is evidence that p53 overexpression does correlate with disease progression,217 which may also be amenable to multiparametric flow analysis.
| |
FOLLICULAR CENTER CELL (FCC) LYMPHOMA |
FCC lymphoma is a relatively well-characterized lymphoma that is derived from B-lineage cells recapitulating features of germinal center cells. FCC lymphomas are the largest group of lymphomas, comprising 45% of all cases.218 These lymphomas arise in lymph nodes, but spread hematogenously early in their course to involve spleen, bone marrow, and occasionally peripheral blood. They are always composed of at least two cell types, small cleaved FCC/centrocytes and large noncleaved FCC/ centroblasts, in varying mixtures.164,219 A grading system based on the relative content of large cells has been proposed that corresponds to the categories of predominantly small, mixed small and large, and predominantly large cell.164 Light scattering properties may help assess the proportion of large cells in a sample, although it has been our experience that large lymphoma cells are more fragile than small cells and thus preferentially lost during preparation.
The phenotype is clonal B-lineage with relatively bright surface Ig. IgM is most common, but all heavy chains may be seen. CD19, 20, and 22 are virtually always present, whereas CD23 and CD10 are frequently but clearly not always present. FCC lymphoma is typically CD5-, CD43-, and CD11c-.164,220 Lack of CD5 and high SIg intensity help distinguish FCC from CLL/SLL and MCL. When CD10 is present, this, with high SIg intensity and absence of CD11c, helps in differentiating FCC from marginal lymphomas. Hairy cell leukemia can usually be recognized by the intense CD20 and the presence of CD11c, CD103, and CD25. The presence of CD10 with CD19 or CD20 and intense clonal light chain can be used to construct multiparameter analyses that can detect residual lymphoma in body fluids with great sensitivity, approaching 1% in our experience. Bone marrow involvement by the predominantly small cleaved cell form is less easily detected because of its paratrabelcular location that is frequently not aspirated. Direct processing of a biopsy sample helps, but does not completely overcome this problem.
FCC lymphomas are associated with a t(14; 18) (q32; q21) in 70% to 95% of cases, resulting in rearrangement of the BCL-2 gene.221-224 BCL-2 rearrangement is rare in CLL, B-PLL, hairy cell leukemia, and splenic lymphoma with villous lymphocytes (SLVL).225 Detection of t(14; 18) by PCR is quite sensitive, generally 1/100,000 cells, and demonstrates circulating cells in the majority of stage I and II patients.221 However, enhanced PCR shows the presence of t(14; 18) in follicular hyperplasia and peripheral blood B cells of normal individuals.226,227 Furthermore, the presence of t(14; 18) at diagnosis does not correlate with outcome in FCC lymphoma224 and t(14; 18) cells in the circulation of stage III and IV patients treated conventionally showed no correlation with clinical remission status or remission duration.228 In autologous marrow transplant patients, PCR detection of t(14; 18) cells in the purged marrow or the patient's marrow after transplantation was associated with increased risk of relapse by some229,230 but not all231 investigators. Additionally, Ig gene rearrangements may not be stable clonal markers in FCC lymphoma because of extensive somatic mutation.232
Secondary chromosomal changes are common in t(14; 18)+ patients and are associated with shorter survival.233 Alterations of p53 on chromosome 17p may be important prognostically.224,234-236 The MYC oncogene may also play a role in progression and transformation of FCC lymphoma.237,238 It may be feasible to assay cells for p53 protein by flow cytometry, but protein levels do not uniformly correlate with p53 mutations.239
| |
MARGINAL ZONE AND RELATED B-CELL LYMPHOMAS |
This section discusses marginal zone lymphomas including extranodal disease of MALT (mucosa-associated lymphoid tissue) type, nodal disease (monocytoid B-cell lymphoma), and the similar but distinct splenic marginal zone lymphoma (SMZL) with and without villous lymphocytes.164 These entities are discussed together because of the significant overlap in immunophenotypes.
Monocytoid B-cell lymphomas240 and MALT lymphomas241 have similar morphologic features and essentially identical immunophenotypes,206 resulting in the proposed term marginal zone B-cell lymphoma to encompass both entities.164 SMZL is clinically distinct, but has a very similar and probably indistinguishable immunophenotype.164
Marginal zone B-cell lymphomas constitute about 10% of stage III/IV lymphomas previously classified as low or intermediate grade (A through E) in the Working Formulation.206 Patients may present with either extranodal or nodal disease. Disease occurs in adults frequently in association with autoimmune disease, particularly Sjogren's syndrome.164,242,243 A typical presentation is with stage I or II extranodal disease. Common sites of involvement are glandular epithelial structures, particularly stomach and salivary gland.164,242 Less common nonmucosal sites include breast, skin, and soft tissue with identical histopathology to the more common sites.164,244 A small number of patients have isolated nodal disease. Transformation to a large-cell higher grade lymphoma may occur, but blood or bone marrow involvement is unusual. Thus, most flow analysis of these lesions will be in lymph node biopsies or FNA's of lymph nodes or tissues. Patients with localized disease have better survival than those with generalized disease.164,206,242
The immunophenotype is that of a postfollicular marginal zone B-cell. Pan-B antigens CD19, CD20, CD22, and HLA-DR with moderate intensity clonal SIg are expressed. The heavy chain is more often IgM than IgG or IgA. Expression of IgD is unusual. Cells are CD5-, CD10-, and CD23- and frequently but not always CD21- and CD24-, which helps distinguish them from CLL/SLL, mantle cell, and FCC disorders. Most but not all cases express CD11c; CD25 is absent, which distinguishes hairy cell leukemia. Molecular studies support the concept that these cells have features of postgerminal center lymphocytes that have undergone antigen selection and may function as memory cells.245 This is interesting in light of their association with autoimmune disease and evidence that early lesions may be antigen driven246 and respond to eradication of the antigen as seen with antibiotic treatment of Helicobacter pylori.247
Approximately 60% of MALT lymphomas have trisomy 3 independent of specific site of origin, further supporting their unification in a single diagnostic entity. In contrast, the incidence is much lower in SMZL, suggesting that they are genetically distinct.248 A minority of SMZL will have BCL-1 rearrangements, but the breakpoints are different from those in MCL.249 BCL-1 and BCL-2 rearrangements are not seen in marginal zone B-cell lymphomas.164
SMZL with and without villous lymphocytes is clinically distinct from marginal zone B-cell lymphoma despite molecular evidence of an origin from postfollicular cells that have undergone antigen selection250 and similar immunophenotype.251 These patients have splenomegaly with peripheral blood and bone marrow involvement usually without lymphadenopathy.252 The differential diagnosis is usually with CLL, MCL, and hairy cell disorders. The immunophenotype is CD19,20, HLA-DR, and strongly CD22+ with clonal SIg of moderate to bright intensity. CD24 is usually positive, whereas CD11c, CD10, CD23, and CD38 are positive in one third to one half of the cases. CD25 is seen in one fourth of the cases, but CD5 and CD103 are usually negative. When the entire phenotype is considered, SMZL can usually be distinguished from CLL, mantle cell leukemia, and hairy cell leukemia, which is crucial because of major differences in prognosis and treatment. Hairy cell variants may be more difficult.251 Our experience is that flow cytometry alone will not reliably distinguish the various marginal zone processes or hairy cell variants but will allow classification as a marginal cell-type disorder.
| |
HAIRY CELL LEUKEMIA |
Hairy cell leukemia is an uncommon but well-recognized chronic B-lineage lymphoproliferative disorder characterized by splenomegaly, pancytopenia, bone marrow infiltration, increased susceptibility to infection, and circulating lymphocytes with abundant pale cytoplasm with hairy projections.
The tumor cells typically express B-lineage antigens CD19, CD20, CD22, and CD79a. They are SIg+ with clonal light chain restriction. All heavy chains have been described, but IgM or IgM and IgD are most common. SIg is of moderate intensity. Hairy cell leukemia is frequently CD21- and typically but not always CD5-, CD10-, and CD23-. CD11c and CD22 are intensely expressed. CD25 is moderately expressed. The immunophenotypic pattern suggests recapitulation of a later B-lineage developmental stage than CLL or PLL. Gene rearrangement analysis supports this concept.253 The mucosal lymphocyte antigen CD103 has been noted to be the most reliable marker for distinguishing hairy cell leukemia from other B-cell leukemias.164,167,254,255 The CD103 epitope appears to be a member of the integrin family that is also expressed on mucosa-associated T cells and some activated lymphocytes.256 Flow cytometric use of this marker allows the detection of minimal residual disease in bone marrow with a sensitivity of less than 1%.257 Immunohistochemistry is also sensitive in the detection of residual disease.258,259 It is not clear from the present data whether the above-mentioned markers will reliably distinguish hairy cell leukemia from certain marginal zone lymphomas and hairy cell variants that represent the greatest problem in our experience. The largest of the above-mentioned studies excluded hairy cell variants.167 It has been our experience and that of others260 that hairy cell variant cases are usually CD25-. This distinction may be important, because most of these variants do not respond as well to standard hairy cell leukemia therapy. One of the very effective therapies for hairy cell leukemia is cladribine (2-chlorodeoxyadenosine).261,262 One complication of cladribine is prolonged suppression of CD4+ T lymphocytes, which can be monitored by flow cytometry.263,264 Interestingly, some investigators report an increased incidence of second neoplasms in patients treated with interferon-, which is another therapy for hairy cell leukemia.265
| |
PLASMA CELL DYSCRASIAS |
Multiple myeloma and other plasma cell disorders have traditionally been difficult to assess by flow cytometry. This is in large part due to the loss of most B-lineage-specific antigens and SIg with maturation to plasma cells. There are few strong specific single-color reagents in general use for differentiated plasma cells, although a relatively strong terminal B-cell-restricted antigen, HM1.24, has been described.266 A recent study used a multiparameter approach with membrane permeabilization and achieved sensitivity less than 1%.267 In our experience, an additional problem is poor representation of plasma cell disorders in marrow aspirates despite obvious morphologic involvement on biopsy. This may be due in part to the focal nature of marrow involvement.
Plasma cells typically express bright CD38 and dim or absent CD45. The use of two-color analysis with CD38 and CD45 will reliably identify plasma cells in peripheral blood and bone marrow.268,269 Clonality may be assessed by three-color analysis with CD45, CD38, and or light chains.268 When a CD38 bright, CD45 low to intermediate profile was combined with low to intermediate orthogonal scatter and intermediate to high forward scatter for sorting, a morphologically pure population of myeloma cells was obtained from bone marrow.269
SIg expression is frequently weak in plasma cells, complicating the distinction of neoplasia from benign reactive proliferations. Cytoplasmic staining using membrane permeabilization after fixation of surface stains is one approach.267 Also, normal plasma cells have been described as CD19+ and CD56-, whereas myeloma cells are CD19- and generally CD56+.270,271 CD40 and CD28 have also been studied for differential expression on normal plasma cells and myeloma cells with mixed results.272
Despite the complexities of assaying plasma cells, relapse in myeloma patients may be more dependent on the presence of circulating clonotypic B lymphocytes expressing P-glycoprotein along with CD19, CD38, and CD56.273,274 These observations are consistent with the derivation of myeloma cells from a less differentiated B-lineage precursor probably under the influence of interleukin-6.269,275 If these hypotheses are correct, then counting bone marrow plasma cells may be an inadequate means of evaluating clinical remission. Although a molecular technique such as allele-specific oligonucleotide PCR is sensitive and specific, it is labor intensive276,277 and not always available. Multiparameter flow cytometry may be able to play a significant role in the evaluation of treatment.
Peripheral blood stem cell transplants have been used in multiple myeloma and are highly dependent on the number of CD34 cells infused per kilogram.278 Fortunately, myeloma cells and their precursors do not appear to be CD34+ and do not sort with CD34 stem cells.279,280
Approximately 5% of patients present with a solitary bone or soft tissue plasmacytoma. The development of FNA techniques in conjunction with flow cytometry improves the likelihood of diagnosis. Thus, routine antibody panels on FNA samples of solid tumors should be able to detect plasma cells. We prefer a two- or three-color analysis using CD45, CD38, and light chains. Recognition of these lesions is important as some may be curable.281,282
Waldenström's macroglobulinemia is a rare low-grade lymphoproliferative disorder characterized by secretion of clonal IgM and a polymorphic infiltrate in bone marrow and other organs consisting of lymphocytes, plasma cells, and plasmacytoid lymphocytes.283-285 Despite the morphologic heterogeneity, the cells are all clonal B-lineage cells of varying stages of differentiation. CD38 is not as bright as myeloma, whereas many B-lineage antigens are brighter than in CLL/SLL or myeloma.284 Surface IgM is usually brighter in Waldenström's than in CLL/SLL, which typically expresses IgM and IgD, whereas myeloma often expresses no heavy chain, although IgG is the most common synthesized. Flow cytometry can be quite important in the distinction of Waldenström's from CLL/SLL, myeloma, or benign reactive conditions.
| |
PERIPHERAL T-CELL DISORDERS |
This group of disorders is characterized by a peripheral T-cell phenotype in contrast to the thymic phenotype of T-ALL and lymphoblastic lymphoma. The major features are CD3 coexpressed with segregated expression of either CD4 or CD8. These neoplasms usually express clonal T-cell receptors, either the - or  - form. Although certain neoplasms are predominantly CD4+ and others are CD8+, these cannot be used as clonal tumor-specific markers. Aberrant phenotypes, particularly loss of pan-T-cell antigens, are very common in this group of disorders. In addition, many peripheral T-cell disorders show alteration of antigen density as detailed below. Many of the leukemic cases were historically called T-CLL, but the vast majority can now be more specifically classified into one of the groups described below.286
In some studies, but not in our experience, the most common leukemic disorder with a postthymic phenotype is T-PLL, accounting for one-third of all cases.287,288 Patients present with leukocytosis (>100,000 frequently), splenomegaly, and lymphadenopathy. The phenotype is usually CD2+, CD3+, CD5+, and CD7+. Most are CD4+, CD8- but can occasionally coexpress CD4 and CD8; CD8 expression alone is less common.287 Abnormalities of chromosome 14 with breakpoints at q11 and q32 are a consistent finding. Patients with the CD4+, CD8- phenotype may respond better to therapy.287 This disorder appears to be more aggressive than B-PLL.287,288
Large granular lymphocytic (LGL) leukemia is a more common disorder than T-PLL in our practice. Cells have the characteristic morphologic features of large granular lymphocytes. Lymphocytosis is mild to moderate with frequent neutropenia.289-292 Two phenotypes are commonly described, although more extensive subdivision has been proposed.293 A T-cell phenotype (T-LGL) exhibits CD3, dim CD8, and CD2 together with some NK cell markers such as CD16, CD11b, and CD57. CD56 is usually negative, as are CD5, CD7, CD4, and CD25.291,292,294 These cases usually show T-cell receptor gene rearrangements and there is a significant association with rheumatoid arthritis.291,292 A less common phenotype is a more classical NK cell (NK-LGL) with CD2, CD56, and CD16. Usually CD3, CD4, TCR - are absent, and CD8 and CD57 are weak or absent. These cases do not exhibit TCR gene rearrangement and have distinct clinical features with more significant anemia, thrombocytopenia, and hepatosplenomegaly.290,292 Both forms are generally indolent, but a CD3+, CD56+ variant of T-LGL appears more aggressive.295 Also, the recently described hepatosplenic - T-cell lymphoma is aggressive and has overlapping morphology with a CD3+, CD56+ phenotype.296,297
Mycosis fungoides (MF ) and the Sézary syndrome (SS) cells are CD4+ and also express CD2, CD3, and CD5. CD7 is sometimes negative. Rare CD8 cases have been described.164 The diagnosis may be difficult in cases without an aberrant phenotype and ambiguous morphology. Demonstration of clonal rearrangements of the TCR gene may be necessary to distinguish lymphoma from benign reactive conditions. A number of new molecular assays may be helpful in both diagnosis and monitoring for minimal residual disease.298-301 MF and SS account for the vast majority of cutaneous lymphomas. The remaining cases are a mixture of B- and T-cell lymphomas of various types.302,303 Although rare, there are reports of human T-cell leukemia virus (HTLV) I and II in patients with MF and SS.304,305
Adult T-cell lymphoma/leukemia, which is HTLV 1-associated,306,307 has an activated T-cell phenotype expressing TCR, CD3, CD4, CD5, HLA-DR, and intense CD25. The cells are usually CD7- and CD8-.308,309 The adhesion molecule L-selectin is also aberrantly overexpressed and can be detected by flow cytometry.310 Abnormalities of p53 may be associated with disease progression.311,312
Lymphoepithelioid (Lennert's) lymphoma is also a CD4+ peripheral T-cell lymphoma.313,314 This lymphoma is not separated from peripheral T-cell lymphomas as a distinct entity by the REAL classification,164 but can be confused morphologically with Hodgkin's disease. It has been our experience that the benign small lymphocytes in Hodgkin's are also CD4+. Thus, unless the lymphoepithelioid lymphoma expresses an aberrant pattern of T-cell antigens, flow cytometry may be of minimal help.
A unique form of peripheral T-cell lymphoma is angiocentric lymphoma, which is characterized by an angiocentric proliferation of small and atypical lymphocytes admixed with plasma cells, eosinophils, and histiocytes. Invasion of blood vessel walls is characteristic. The disease is frequently extranodal, most often involving the lung. The phenotype is CD4+ postthymic with frequent aberrant features. There may be clonal rearrangement of TCR genes, but consistent cytogenetic changes have not been described. Some cases may be related to Epstein-Barr virus (EBV).315-319 Also related to EBV is angioimmunoblastic lymphadenopathy type T-cell lymphoma, which also shows a peripheral CD4+ T-cell phenotype with systemic symptoms related to cytokine production.164,320 Remaining cases of large-cell lymphoma with a peripheral T-cell phenotype are discussed in the large-cell lymphoma section.
The remaining cases of unclassified chronic lymphoid leukemias with a peripheral T-cell phenotype represent less than 1% of the total cases. The cells may appear morphologically similar to typical CLL; however, the clinical course is more aggressive. Most cases are CD2, CD3, CD5, CD7, and CD4+, with a minority CD8+. Aberrant patterns are not seen.321 These cases may represent a T-cell form of CLL, but it appears that they may have a distinct clinical course. We recommend that they be classified separately from CLL. A summary of low-grade T-cell lymphoproliferative disorders is presented in Table 4.
The peripheral T-cell disorders can be difficult to distinguish, with overlapping morphology and immunophenotypes. Cytogenetics may help in separating low- and high-grade lesions.322 Ultimately, diagnosis must be based on a combined approach. Distinction of different peripheral T-cell neoplasms is crucial because of the wide range in therapy from minimal323 or none to bone marrow transplantation324 and the equally wide range in response by different disorders to a given therapy.325
| |
LARGE-CELL LYMPHOMA (LCL) |
This section discusses LCL that have not been reviewed under a specific section such as peripheral T-cell disorders. LCL are encountered in lymph node biopsies, fine needle aspirates of lymph nodes or masses, bone marrow aspirates, and rarely in peripheral blood. We have found the cells of LCL to be particularly fragile compared with background lymphocytes and thus frequently underrepresented, particularly in fine needle aspirates. In some cases, fragmented cells with interpretable staining patterns may be recovered in the low forward, low side scatter gating area or by back gating with lineage markers. Preservation of tissues and fluids may be enhanced with cell culture medium.
LCL account for 40% of lymphomas in adults326 and one third of cases in children.327 In adults, 80% are B-cell,328 whereas, in children, LCL are equally divided between T-cell, B-cell, and indeterminate phenotypes, with a significant percentage (40%) of CD30+ cases.327
Immunophenotype is helpful in confirming the diagnosis of LCL, frequently excluding carcinoma or other types of hematopoietic malignancy. However, in adults, it has not been consistently associated with prognostic differences, although there are data suggesting that the T-cell form may do worse.329 Elevation of S-phase fraction may identify more aggressive disease.330,331 In children, there does appear to be an independent survival advantage for the B-cell phenotype. BCL-6 gene rearrangements are frequent in LCL and are associated with a B-cell phenotype and better clinical outcome.326,332 A potentially confusing group of patients are those with T-cell-rich B-cell lymphomas. These are clinically similar to other large B-cell lymphomas and should be treated as such.333,334 Immunophenotyping may be essential to prevent confusion with Hodgkin's disease and peripheral T-cell lymphomas.335
Another source of confusion is that diffuse LCL of B-cell type are not infrequently SIg-. B-lineage antigens such as CD19, CD20, and CD22 are more reliable markers and the inability to demonstrate light chain clonality does not necessarily exclude malignancy. A distinct subgroup of LCL, primary mediastinal B-cell lymphomas, although uniformly expressing B-lineage antigens such as CD20, are frequently SIg-.336,337 The large-cell size, morphology, and lack of CD34 or TdT should exclude lymphoblastic lymphoma.
An important subgroup of patients with LCL are those that are CD30+ and are associated, although not uniformly, with an anaplastic large-cell morphology.338 Anaplastic large-cell lymphoma (ALCL) has been a controversial entity in that other lymphomas and Hodgkin's disease may have CD30+ cells.338,339 ALCL are either B- or T-cell or non-T, non-B phenotype; the T-cell phenotype is the most common, especially in children.339-341 Expression of activation antigens such as CD25, Cdw70, CD71, and HLA-DR are common.339 Bone marrow involvement is infrequent, but extranodal disease, particularly of the skin, is common.338-341 The systemic form must be distinguished from a primary cutaneous form that has a more favorable outcome.339,342-344 ALCL must be distinguished from Hodgkin's disease, carcinoma, and sarcomas. Phenotype together with morphology and clinical picture are necessary for diagnosis. The presence of a t(2; 5)(p23; q35) is common in ALCL, especially with a T-cell or non-B-cell, non-T-cell type. It is usually not seen in Hodgkin's disease, but may be seen in immunoblastic and other large-cell lymphomas.345-347
| |
HODGKIN'S DISEASE |
Hodgkin's disease is a distinct type of malignant lymphoma that differs from other tumors in that typically less than 1% of the cells present are neoplastic cells that are morphologically recognizable. The majority of the cells are nonmalignant inflammatory cells. As a consequence, most cases show a nonspecific reactive pattern by flow cytometry. This greatly limits the utility of flow cytometry in Hodgkin's disease. It has been difficult to study the clonality and the nature of the neoplastic Reed-Sternberg cells and their variants. T- and B-cell markers as well as clonal rearrangements of Ig and T-cell receptor genes have been reported.348-356 In one study, single Reed-Sternberg cells from patients with Hodgkin's disease with a B-cell immunophenotype were stained for CD30 and rearranged VH genes of these cells were amplified by the PCR and analyzed by gel electrophoresis and nucleotide sequencing.357 Rearranged VH genes were identified in all cases, demonstrating that the Reed-Sternberg cells arose from B cells. In six of the patients studied, the Reed-Sternberg cells were polyclonal and the remaining six cases were monoclonal or mixed cell populations. In another study of single cells, polyclonal populations of Reed-Sternberg cells were identified,358 whereas in a different study only monoclonal tumor cells were identified.359 Clonal chromosomal abnormalities are common in Reed-Sternberg cells; numerical abnormalities characterize most cases,360-364 but structural changes are also reported without a single predominate translocation. In one study,365 23 of 28 patients showed abnormal metaphases and 14q32 abnormalities were found in six cases; however, t(14; 18) was infrequent.
Immunophenotypic studies on Reed-Sternberg cells from patients with nodular sclerosing, mixed cellularity, and lymphocyte-depleted Hodgkin's disease show CD30, CD70 and CD15 positivity. They are typically CD45-. We have used two-color flow analysis with CD15/CD30 to identify Reed-Sternberg cells in occasional patients, but the sensitivity has been quite poor. T-cell markers such as CD2, CD3, and CD4 are reported in nearly half of the cases.349-351,366 B-cell markers including CD19, CD20, and CD22 are less commonly seen in these subtypes.349,353,354 Nodular lymphocyte predominant Hodgkin's disease is considered a distinct B-cell subtype.367 Reed-Sternberg cells from nodular lymphocyte predominant Hodgkin's disease express CD20,368 the B-cell-specific J chain,369 and CD45, but do not express CD30, CD70, or CD15. Cell activation markers that may be found on Reed-Sternberg cells include CD25, HLA-DR, and CD71.349,352,366,370 The B7/BB1 molecule that is found on antigen-presenting cells and is the natural ligand for CD28 and CTLA-4 on T cells is strongly expressed on Reed-Sternberg cells.371 CD40, which is a member of the tumor necrosis factor receptor superfamily and is expressed on a variety of antigen-presenting cells as well as other cells, is also found at high levels on Reed-Sternberg cells.372
Despite the considerable information on the phenotype of Reed-Sternberg cells, most cases of Hodgkin's disease studied by flow cytometry will only show a mixed but mostly T-cell lymphocytic component, usually CD4 predominant.373 We have seen a CD8 predominant pattern in a case of T-cell-rich B-cell lymphoma similar to a recent case report.374 This variant of LCL requires different therapy, but may be morphologically very similar to lymphocyte-rich Hodgkin's.335
| |
HISTIOCYTIC NEOPLASMS |
The term histiocyte refers to tissue based cells of both the monocyte-macrophage and Langerhans'-dendritic cell lineage. Both lines derive from a CD34+ bone marrow stem cell and involve a circulating peripheral blood precursor.375 These two lines share many surface markers, including HLA-DR, CD11, CD18, CD33, CD45, CD16 (Fc receptor for IgG), and the granulocyte-macrophage colony-stimulating factor (GM-CSF ) receptor. They differ in the greater monocyte/macrophage expression of CD15, CD54, and CD68 and by the Langerhans'/dendritic cell's expression of CD1a and S-100.375 However, the most distinctive features are the presence of significant phagocytosis by macrophages and the presence of the CD1a complex and Birbeck granules in Langerhans' cells.376
The nomenclature of malignant disorders of histiocytes has been clouded by the use of multiple terms and the inability to always distinguish reactive from malignant proliferations. Unfortunately, there are no markers of clonality unique to histiocytes. In 1985, the Histiocyte Society proposed the term Langerhans' cell histiocytosis (LCH) to replace malignant acute and chronic histiocytosis-X, which had included the prior terms Letterer-Siwe disease, Hand-Schuller-Christian disease, and eosinophilic granuloma.377,378 This group of disorders is characterized by proliferation of Langerhans' cells and a wide clinical spectrum. In 1994, it was shown with X-linked DNA probes that several forms of Langerhans' cell histiocytosis contain clonal histiocytes and thus may represent a clonal neoplastic disorder.379,380 Langerhans' cell histiocytosis is the major neoplasm of the Langerhans/dendritic (antigen-presenting) cell line. A definitive diagnosis of LCH requires the demonstration of CD1a or Birbeck granules.381
Malignant proliferations of phagocytic histiocytes are extremely rare.375,382 Several benign proliferations include reactive and familial hemophagocytic syndromes, storage diseases, Rosai-Dorfman disease, and Kikuchi's disease. Malignancies of blood and bone marrow precursors are discussed with the acute leukemias. Malignant histiocytosis and true histiocytic lymphoma are extremely rare and remain controversial. Syndromes that mimic malignant histiocytosis have been described in lymphomas, particularly T-cell type, in which elaboration of lymphokines drives the histiocytic component.383,384 A small number of cases, mainly in children, of malignant histiocytosis contain a 5q35 rearrangement and appear to represent a true histiocytic neoplasm.375
The role of flow cytometry has been relatively limited, because most of these disorders are tissue-based. However, with the increasing use of flow cytometry in lymph node biopsies and fine needle aspirates, histiocytic proliferations may be encountered. Histiocytic differentiation can be recognized by the presence of HLA-DR, CD14, CD11c, CD45, weak CD33, and CD4. Cells will be large with moderate amounts of side scatter. The absence of specific B- and T-lineage markers is an important adjunct. Flow cytometry cannot reliably distinguish LCH and malignant histiocytosis from reactive proliferations of histiocytes. The presence of CD1a or Birbeck granules are the definitive features of LCH, but Birbeck granules may not be detectable in all cases and flow cytometry for CD1a may show a wide range in the percentage of positive cells.385 Flow cytometric demonstration of an aberrant T-cell population would be very helpful in recognizing a T-cell lymphoma with secondary proliferation and activation of histiocytes that may mimic malignant histiocytosis.
| |
APLASTIC ANEMIA AND MYELODYSPLASTIC SYNDROMES (MDS) |
Flow cytometry is not used in aplastic or dysplastic disorders to the same degree as in leukemias and lymphomas, but is important for certain limited applications. Samples are almost always blood or bone marrow.
Patients with maturational abnormalities of bone marrow usually characterized by peripheral cytopenia in the setting of an adequately cellular or hypercellular marrow are considered to have primary MDS after the exclusion of certain reversible causes with a similar picture such as folate or vitamin B12 deficiencies. Approximately 15% to 20% of MDS patients will evolve into AML.386 The risk of acute leukemia and prognosis are related to the percentage of blasts in the marrow and the presence of underlying cytogenetic abnormalities.386,387 Flow cytometry may be useful in determining the percentage of blasts using either the CD45 side scatter plot or measuring CD34+ cells. AML arising in a MDS setting generally is phenotypically similar to de novo AML. However, the presence of lineage heterogeneity388 and lymphocyte activation antigens CD25 and CD30 are common.389
Aplastic anemia also presents with peripheral cytopenia, but is associated with a markedly hypocellular marrow. Traditionally a devastating disease, remarkable advancement has been made in therapy. Although bone marrow transplantation is curative for some patients, others may respond to immunosuppressive regimens.390 Many patients with aplastic anemia suffer from immune-mediated destruction of CD34+ progenitors, possibly through Fas-mediated apoptosis facilitated by activated T-cell release of cytokines such as interferon- and tumor necrosis factor-.390-392 Flow cytometry shows increased levels of HLA-DR+, CD8+ lymphocytes and CD56+ NK cells in the marrow.393 These findings may not be reflected in the peripheral blood; thus, study of bone marrow may be important in identifying patients with immune-mediated aplastic anemia.393
In children, aplastic anemia may precede the onset of ALL.394-398 This presentation is most common in young females, often in association with an infectious illness,395 and represents 1% to 2% of pediatric ALL.394-398 Cytogenetics are frequently normal in the aplastic marrows, even though they are abnormal in the subsequent leukemia.394 We have seen a child with t(4; 11) translocation associated ALL preceded by an aplastic episode in which cytogenetics were normal but flow cytometry showed an aberrant lymphoid population that was CD15+ and phenotypically identical to the subsequent leukemia clone. Children with aplastic anemia should be evaluated thoroughly with consideration of the possibility of an ALL prodrome.
Paroxysmal nocturnal hemoglobinuria (PNH) is a rare acquired clonal dysplastic disorder in which the patient's red blood cells exhibit excessive sensitivity to complement. Although the classic presentation is nocturnal hemolysis, more often patients present with pancytopenia or unexplained recurrent thrombosis. The basic deficit is failure to properly synthesize the major anchoring protein glycosylphosphatidyl-inositol (GPI). The sensitivity to complement is explained by the inability to anchor complement regulating proteins CD55 and CD59. The risk of thrombosis presumably relates to other GPI-linked proteins. The deficiency of CD59 is demonstrated by flow cytometry.399 There is some evidence CD66c may be more sensitive than CD59 in detecting deficient GPI-anchored proteins.400
| |
DISEASE MONITORING |
This section will briefly describe the rapidly emerging use of flow cytometry in the monitoring of disease. For more extensive discussion see the reviews cited below.
Detection of minimal residual disease (MRD).
Flow cytometric detection of MRD in acute leukemia and other hematologic malignancies has recently been reviewed.401-405 Typically, light scatter is combined with multiparameter staining for tumor-specific antigen combinations.83,401-407 Analytical sensitivity using such technology is in the range of one neoplastic cell for every 103 to 104 normal cells.408,409 There exist rare exceptions in which a single antibody may specifically recognize malignant cells, such as the 7.1 antibody that recognizes a unique surface protein found on childhood ALL cells with translocations and inversions of chromosome 11q.410 With the addition of technologies to fix cells for permeabilization, intracellular antigens can also be detected by flow cytometry.411,412 Tissues that can be studied include bone marrow, peripheral blood, cerebral spinal fluid, or any other body fluid. The strategy of detecting malignant cells using expression of aberrant phenotypes rarely found normally requires thorough knowledge of the frequency of normal patterns of expression as recently described for bone marrow.413 Additionally, certain markers such as TdT are only expressed in T cells that reside in the thymus and a limited number of bone marrow cells. The majority of cases of ALL and lymphoblastic lymphoma express TdT. Therefore, if TdT+ cells are found in the peripheral blood or cerebrospinal fluid, one can identify them as malignant cells.
The majority of B-lineage ALL cells express TdT, CD19, and CD10, with a smaller number expressing CD34. Any combination of these markers (all of which are found on normal cells in the bone marrow) with the addition of certain aberrant markers such as CD13, CD33, or CD15 may uniquely identify the ALL cells from normal bone marrow or peripheral blood cells. TdT can be studied with T-cell markers such as CD5, CD7, or cytoplasmic CD3 to detect cases of T-ALL.414,415 An increasing percentage of abnormal cells in two consecutive samples using this approach yielded a clinical sensitivity of 92% and specificity of 75% for relapse in one study of ALL.416 For AML, a variety of combinations of markers, including CD34 with CD56, AML that expresses TdT, and cases of AML that coexpress lymphoid antigens (ie, CD7 and CD19), combined with light scatter and antigen density allow for the sensitive identification of AML in most cases.29,417-420 In one report, coexpression of CD19 and CD56 was found on 9 of 16 cases of childhood AML of the FAB M2 subtype with t(8; 21) and not in any of the additional 14 cases studied.50
There exist minimal data for chronic lymphoproliferative diseases. For hairy cell leukemia using two-color flow cytometry, sensitivity to less than 1% of hairy cells among circulating cells can be detected.167 Some of these markers include coexpression of CD103 and CD22, intense uniform expression of CD11c with CD19, and moderate intense staining for CD25 with CD19. The expression of CD11c is 30-fold higher in intensity on hairy cells than CLL/SLL cells, and the intensity of CD25 is sixfold higher on hairy cell leukemia cells than on CLL/SLL cells. In aggregate, these dual markers are unique for hairy cell leukemia, with coexpression of CD103 and CD22 being the most specific.
CLL can also be identified in the peripheral blood and bone marrow by flow cytometry. Coexpression of CD5 with either CD20 or CD19187 or CD5 with and light chain421 may detect minimal residual disease to less than 5% sensitivity. Three-color flow analysis using CD5, CD20, or CD19 with and may increase this sensitivity to less than 1% (Fig 2). In one study, achievement of no residual disease by dual parameter staining in complete clinical responders was highly predictive of time to progression.421
Perhaps a more critical question is whether sensitive in vitro identification of MRD has prognostic importance. In one study using double-color analysis detecting CD5 and TdT for patients with T-ALL, 11 of 12 relapses were detected 4 to 21 weeks before morphologic diagnosis of relapse406; 16 patients without detectable CD5 and TdT double-labeled cells were in remission during 43 months of follow-up. In an AML study, 12 TdT+ AML cases were studied and 9 of 10 relapses were detected by immunophenotypic identification before morphologic relapse422; patients without immunophenotypic identification of cells remained in complete remission for 32 to 46 months of follow-up. In another study, 13 children in complete remission after bone marrow transplantation were observed and the 4 patients with detectable leukemia cells by flow cytometry relapsed within 2 months after the positive cells were identified.401,409 Seven of nine patients without detectable disease remained in remission with a median follow-up of more than 1 year posttransplantation. Detection of neoplastic cells, whether by flow cytometry or molecular methods, at a single point posttherapy probably does not predict relapse as reliably as changing values over time.423,424 Another critical question regarding highly sensitive methods is whether complete eradication of the neoplastic clone is necessary. This topic has recently been discussed in regard to molecular methods of detection,424,425 which have been shown by several investigators to give positive results in healthy individuals or patients with stable long-term remission.426-431 Multiparameter flow cytometry is quantitative, rapid, and relatively inexpensive, with a generally high predictive value for relapse, making it a logical and promising tool in the assessment of MRD.403
View larger version (25K):
[in this window]
[in a new window]
| Fig 3.
Characterization of viable versus apoptotic cells by a dual staining flow cytometry technique. Resting, murine B cells were cultured either without stimulant (A) or with 50 µg/mL lipopolysaccharide for 48 hours. The cells recovered at 48 hours were dually stained with Hoechst 3342 and merocyanine 540 (MC540) as described460 and the cells were analyzed on a FACS Star Plus flow cytometer (Becton Dickinson, San Jose, CA). Dual parameter dot plots enabled the identification of five distinct subpopulations defined as follows: R1, cells with 2n DNA that were MC540 negative/dull (red dots); R2, cells with greater than 2n DNA that were MC540 negative/dull (green dots); R3, cells with 2n DNA that were MC540 bright (blue dots); R4, cells with greater than 2n DNA that were MC540 bright (brown dots); and R5, cells that displayed reduced Hoechst 33342 staining and were either G0 /G1 (R1) or S/M/G2 (R2) cell cycle stages. The R3 and R4 subgroups represent cells in early stages of apoptosis, whereas the R5 subgroup represents fragmenting apoptotic cells. Most techniques for evaluating percentages of apoptotic cells detect only the cells localized to the R5 subgroup. Figure courtesy of E. Charles Snow, PhD.
|
|
Response to therapy.
An exciting and important new use of flow cytometry is the evaluation of tumor response to therapy. Several parameters are available that rely on different aspects of tumor biology.
Expression of the multidrug resistance protein (MDR1), also termed P-glycoprotein (PgP), can be assessed by flow cytometry.432 This membrane pump eliminates many chemotherapeutic agents from cells and may convey drug resistance. Flow cytometry provides advantages over immunohistochemical staining and MDR1 mRNA detection by PCR because of its quantitative and multiparametric capability.432 However, there are many technical controversies associated with detection of PgP/MDR1, as summarized by a recent consensus conference.432 PgP/MDR1 has recently been shown, along with cytogenetic profile and secondary versus de novo disease, to correlate highly with response to therapy in elderly AML patients.433 In this study, MDR1-, de novo AML patients with favorable/intermediate cytogenetics had a complete remission (CR) rate of 81%, whereas patients with MDR1+ secondary AML with unfavorable cytogenetics had a CR rate of only 12%.433 Expression of CD34 in AML is also associated with the MDR phenotype.433-435 This association may partly explain the correlation of CD34 with poor survival previously reported.42,43,45 Other flow methods quantitate the uptake and retention of fluorescent drugs or dyes432,435-437 or assess in vitro drug sensitivity.409 Whereas some of the newer dyes are more sensitive and specific for MDR1, dye/drug efflux does not completely correlate with expression of PgP/MDR1.432,433,435 This may relate in part to other drug resistance proteins such as multidrug resistance-associated protein (MRP) and lung resistance protein (LRP), which may also be assessed by flow cytometry.438-442
Once a chemotherapeutic agent has entered a cell, it exerts its lethal effect in large part by inducing apoptosis. Thus, another emerging field is correlation of resistance to apoptosis with poor response to chemotherapy.443 The BCL-2 and p53 proteins are the most extensively characterized modulators of cancer cell apoptosis443,444 and may be assessed by flow cytometry. Both p53 mutations, which may alter p53 half life resulting in elevated protein levels,445 and BCL-2 protein expression are associated with poor response to therapy in hematologic malignancies.446,447 The important role of p53 in hematologic malignancies has been reviewed extensively and is intimately related to its regulation of cell cycle-specific growth arrest and apoptosis in the setting of DNA damage such as that induced by chemotherapy.445,448 The BCL-2 gene is also an important regulator of apoptosis and is actually a member of a family of genes (BAX and BCL-X) capable of accelerating or inhibiting cell susceptibility to apoptosis.449 BCL-2 is capable of blocking chemotherapy-induced apoptosis in leukemic cells.450 The Fas receptor (FasR, CD95) is another important regulator that induces apoptosis when bound by its ligand FasL.451 The complexity of apoptosis regulation suggests that measurement of a single constituent such as BCL-2 or FasR may not be sufficient. By virtue of its multiparameter capabilities, flow cytometry is ideally suited to assess apoptotic regulatory status. A recent study of BCL-2 and Fas in normal marrow and hematologic malignancy found consistent patterns of expression in normal marrow but great heterogeneity in the malignancies.451 Another study, with treatment implications, suggests that FasR-mediated apoptosis may be cell cycle dependent, occurring predominantly in the G1B compartment.452 Thus, assessment of apoptosis should ideally reflect its relation to the cell cycle as well. As previously discussed, assessment of DNA content and cell cycle kinetics provides prognostic information for AML453 and ALL.454,455 Again, the multiparametric capability of flow cytometry is well suited to this task.456
Detection of apoptosis can be accomplished by measuring changes in DNA using viable dyes such as Hoechst 33342 (Ho342) that do not require membrane disruption.457 This allows simultaneous characterization of specific membrane changes such as the appearance of phosphatidylserine, which occurs early in cells committed to apoptotic pathways.458 The redistribution of phosphatidylserine is detected by staining with either Annexin V459 or merocyanine 540 (MC540).457 A recent report describes a multiparameter technique to simultaneously assess cell cycle and early apoptosis.460 This method allows separation of viable cells from early apoptosis-committed cells with either 2N or 4N DNA content (Fig 3). Because both Ho342 and MC540 are viable dyes, cells may be sorted for further analysis.
This last section has given just a glimpse of the future applications of multiparameter flow cytometry. The ability to sort cells with specific features opens the door to molecular analysis of highly defined populations. Whether it is analyzing the complex surface markers of a lymphoid malignancy or the cytoplasmic pattern of apoptosis regulation, flow cytometry has become far more than a number in the past decade. More than ever, it provides a pattern of information that must be interpreted by a knowledgeable professional in the context of the clinical situation.
| |
FOOTNOTES |
Submitted October 4, 1996;
accepted May 28, 1997.
Address reprint requests to Kenneth A. Foon, MD, Markey Cancer Center, Room CC140, 800 Rose St, Lexington, KY 40536-0093.
| |
ACKNOWLEDGMENT |
The authors gratefully acknowledge the expert assistance of Debbie Brown and Kim Holt in preparation of the manuscript, the expert skills of Ellen Green in editing and preparation of the references and tables, and Barry Grimes in the preparation of the Figs 1 and 2.
| |
REFERENCES |
1.
Foon KA,
Todd RF III:
Immunologic classification of leukemia and lymphoma.
Blood
68:1,
1986[Abstract/Free Full Text]
2.
Jennings CD,
Foon KA:
Flow cytometry: Recent advances in diagnosis and monitoring of leukemia.
Cancer Invest
15:384,
1997[Medline]
[Order article via Infotrieve]
3.
Drouet M,
Lees O:
Clinical applications of flow cytometry in hematology and immunology.
Biol Cell
78:73,
1993[Medline]
[Order article via Infotrieve]
4.
Macy MG:
Flow-cytometric analysis of lymphocytes, leukemias and lymphomas.
Br J Biomed Sci
50:334,
1993[Medline]
[Order article via Infotrieve]
5.
Maeda K,
Alessio RC,
Hawley RC:
Recent advances in diagnosis of leukemia.
Jpn J Clin Oncol
23:79,
1993[Abstract/Free Full Text]
6.
Johnson RL:
Flow cytometry: From research to clinical laboratory applications.
Clin Lab Med
13:831,
1993[Medline]
[Order article via Infotrieve]
7.
Kipps TJ,
Meisenholder G,
Robbins BA:
New developments in flow cytometric analyses of lymphocyte markers.
Clin Lab Med
12:237,
1992[Medline]
[Order article via Infotrieve]
8.
Vaickus L,
Ball ED,
Foon KA:
Immune markers in hematology malignancies.
Crit Rev Oncol Hematol
11:267,
1991[Medline]
[Order article via Infotrieve]
9.
Foon KA,
Robbins BA,
Ellison DJ,
Vaickus L:
Immunodiagnosis of lymphoid malignancies.
Adv Leuk Lymphoma
3:3,
1992
10.
Borowitz MJ:
Immunophenotyping of acute leukemia by flow cytometry.
Clin Immunol Newsletter
13:53,
1993
11.
Schumacher HR,
Shrit MA,
Kowal-Vern A,
Dizikes G,
Radvany RM,
Le Beau MM:
Acute leukemia and related entities. Impact of new technology.
Arch Pathol Lab Med
115:331,
1991[Medline]
[Order article via Infotrieve]
12.
Freedman AS:
Cell surface antigens in leukemias and lymphomas.
Cancer Invest
14:252,
1996[Medline]
[Order article via Infotrieve]
13.
Bene MC,
Castoldi G,
Knapp W,
Ludwig WD,
Matutes E,
Orfao A,
van't Veer MB:
Proposals for the immunological classification of acute leukemias. European Group for the Immunological Characterization of Leukemias (EGIL).
Leukemia
9:1783,
1995[Medline]
[Order article via Infotrieve]
14.
Borowitz MJ,
Guenther KL,
Shults KE,
Stelzer GT:
Immunophenotyping of acute leukemia by flow cytometric analysis. Use of CD45 and right-angle light scatter to gate on leukemic blasts in three-color analysis.
Am J Clin Pathol
100:534,
1993[Medline]
[Order article via Infotrieve]
15.
Cheson BD,
Cassileth PA,
Head DR,
Schiffer CA,
Bennett JM,
Bloomfield CD,
Brunning R,
Gale RP,
Grever MR,
Keating MJ,
Sawitsky A,
Stass S,
Weinstein H,
Woods WG:
Report of the National Cancer Institute-Sponsored Workshop on definitions of diagnosis and response in acute myeloid leukemia.
J Clin Oncol
8:813,
1990[Abstract]
16.
Terstappen LW,
Konemann S,
Stafford M,
Loken MR,
Zurlutter K,
Buchner T,
Hiddemann W,
Wormann B:
Flow cytometric characterization of acute myeloid leukemia. Part I. Significance of light scattering properties.
Leukemia
5:315,
1991[Medline]
[Order article via Infotrieve]
17.
Harada N,
Okamura S,
Kubota A,
Shimoda K,
Ikematsu W,
Kondo S,
Harada M,
Niho Y:
Analysis of acute myeloid leukemia cells by flow cytometry introducing a new light-scattering classification.
J Cancer Res Clin Oncol
120:553,
1994[Medline]
[Order article via Infotrieve]
18.
Franzman C,
Bennett JM:
Classification of acute leukemias.
Contemp Oncol
2:46,
1992
19.
Drexler HG:
Classification of acute myeloid leukemias: A comparison of FAB and immunophenotyping.
Leukemia
1:697,
1987[Medline]
[Order article via Infotrieve]
20.
Bernier M,
Massey M,
Deleeuw N,
Bron D,
Debusscher L,
Stryckmans P:
Immunological definition of acute minimally differentiated myeloid leukemia (M0) and acute undifferentiated leukemia (AUL).
Leuk Lymphoma
18:13,
1995
21.
Creutzig U,
Harbott J,
Sperling C,
Ritter J,
Zimmermann M,
Loffler H,
Riehm H,
Schellong G,
Ludwig WD:
Clinical significance of surface antigen expression in children with acute myeloid leukemia: Results of Study AML-BFM-87.
Blood
88:3097,
1995
22.
Smith FO,
Lampkin BC,
Versteeg C,
Flowers DA,
Dinndorf PA,
Buckley JD,
Woods WG,
Hammond GD,
Bernstein ID:
Expression of lymphoid-associated cell surface antigens by childhood acute myeloid leukemia cells lacks prognostic significance.
Blood
79:2415,
1992[Abstract/Free Full Text]
23.
Kuerbitz SJ,
Civin CI,
Krischer JP,
Ravindranath Y,
Steuber CP,
Weinstein HJ,
Winick N,
Ragab AH,
Gresik MV,
Crist WM:
Expression of myeloid-associated and lymphoid-associated cell-surface antigens in acute myeloid leukemia of childhood: A pediatric oncology group study.
J Clin Oncol
10:1419,
1992[Abstract/Free Full Text]
24.
Bradstock K,
Matthews J,
Benson E,
Page F,
Bishop J,
the Australian Leukaemia Study Group:
Prognostic value of immunophenotyping in acute myeloid leukemia.
Blood
84:1220,
1994[Abstract/Free Full Text]
25.
Sperling C,
Seibt-Jung H,
Gassmann W,
Komischke B,
Sauerland C,
Hiddemann W,
Loffler H,
Buchner T,
Thiel E,
Ludwig WD:
Immunophenotyping of acute myeloid leukemia: Correlation with morphological characteristics and therapy response.
Recent Results Cancer Res
131:381,
1993[Medline]
[Order article via Infotrieve]
26.
Ball ED,
Davis RB,
Griffin JD,
Mayer RJ,
Davey FR,
Arthur DC,
Wurster-Hill D,
Noll W,
Elghetany MT,
Allen SL,
Rai K,
Lee EJ,
Schiffer CA,
Bloomfield CD:
Prognostic value of lymphocyte surface markers in acute myeloid leukemia.
Blood
77:2242,
1991[Abstract/Free Full Text]
27.
Martinez-Climent JA,
Lane NJ,
Rubin CM,
Morgan E,
Johnstone HS,
Mick R,
Murphy SB,
Vardiman JW,
Larson RA,
LeBeau MM,
Rowley JD:
Clinical and prognostic significance of chromosomal abnormalities in childhood acute myeloid leukemia de novo.
Leukemia
9:95,
1995[Medline]
[Order article via Infotrieve]
28.
Cuneo A,
Michaux JL,
Ferrant A,
Van Hove L,
Bosly A,
Stul M,
Cin PD,
Vandenberghe E,
Cassiman JJ,
Negrini M,
Piva N,
Castoldi G,
Van Den Berghe H:
Correlation of cytogenetic patterns and clinicobiological features in adult acute meloid leukemia expressing lymphoid markers.
Blood
79:720,
1992[Abstract/Free Full Text]
29.
Reading CL,
Estey EH,
Huh YO,
Claxton DF,
Sanchez G,
Terstappen LWMM,
O'Brien MC,
Baron S,
Deisseroth AB:
Expression of unusual immunophenotype combinations in acute myelogenous leukemia.
Blood
81:3083,
1993[Abstract/Free Full Text]
30.
Cline MJ:
The molecular basis of leukemia.
N Engl J Med
330:328,
1994[Free Full Text]
31.
Melo JV:
The diversity of BCR-ABL fusion proteins and their relationship to leukemia phenotype.
Blood
88:2375,
1996[Free Full Text]
32.
Second MIC Cooperative Study Group:
Morphologic, immunologic, and cytogenetic (MIC) working classification of the acute myeloid leukemias.
Br J Haematol
68:487,
1988[Medline]
[Order article via Infotrieve]
33.
Catovsky D,
Matutes E:
The classification of acute leukaemia.
Leukemia
6:1,
1992
34.
Bennett JM,
Catovsky D,
Daniel MT,
Flandrin G,
Galton DAG,
Gralnick HR,
Sultan C:
Proposal for the recognition of minimally differentiated acute myeloid leukaemia (AML-MO).
Br J Haematol
78:325,
1991[Medline]
[Order article via Infotrieve]
35.
Venditti A,
Del Poeta G,
Buccisano F,
Tamburini A,
Cox MC,
Stasi R,
Bruno A,
Aronica G,
Maffe L,
Suppo G,
Simone MD,
Forte L,
Cordero V,
Postorino M,
Tufilli V,
Isacchi G,
Masi M,
Papa G,
Amadori S:
Minimally differentiated acute myeloid leukemia (AML-M0): Comparison of 25 cases with other French-American-British subtypes.
Blood
89:621,
1997[Abstract/Free Full Text]
36.
Stasi R,
Poeta GD,
Venditti A,
Masi M,
Stipa E,
Dentamaro T,
Cox C,
Dallapiccola B,
Papa G:
Analysis of treatment failure in patients with minimally differentiated acute myeloid leukemia (AML-M0).
Blood
83:1619,
1994[Abstract/Free Full Text]
37. Poeta GD, Stasi R, Vendiiti A, Masi M, Papa G: CD7 expression in acute myeloid leukemia. Blood 82:2929, 1993 (letter)
38.
Kita K,
Miwa H,
Nakase K,
Kawakami K,
Kobayashi T,
Shirakawa S,
Tanaka I,
Ohta C,
Tsutani H,
Oguma S,
Kyo T,
Dohy H,
Kamada N,
Nasu K,
Uchino H (The Japan Cooperative Group of Leukemia/Lymphoma):
Clinical importance of CD7 expression in acute myelocytic leukemia.
Blood
81:2399,
1993[Abstract/Free Full Text]
39.
Yumura-Yagi K,
Hara J,
Kurahashi H,
Okamura J,
Koizumi S,
Toyoda Y,
Murayama N,
Inoue M,
Ishihara S,
Tawa A,
Nishiura T,
Kaneyama Y,
Okada S,
Kawa-Ha K:
Clinical significance of CD7-positive stem cell leukemia.
Cancer
68:2273,
1991[Medline]
[Order article via Infotrieve]
40.
Osada H,
Emi N,
Ueda R,
Seto M,
Koike K,
Suchi T,
Kojima S,
Obata Y,
Takahashi T:
Genuine CD7 expression in acute leukemia and lymphoblastic lymphoma.
Leuk Res
14:869,
1990[Medline]
[Order article via Infotrieve]
41.
Schwarzinger I,
Valent P,
Koller U,
Marosi C,
Schneider B,
Haars O,
Knapp W,
Lechner K,
Bettleheim P:
Prognostic significance of surface marker expression on blasts of patients with de novo acute myeloblastic leukemia.
J Clin Oncol
8:423,
1990[Abstract]
42.
Borowitz MJ,
Gockerman JP,
Moore JO,
Civin CI,
Page SO,
Robertson J,
Bigner SH:
Clinicopathologic and cytogenetic features of CD34 (MY10)-positive acute nonlymphocytic leukemia.
Am J Clin Pathol
91:265,
1989[Medline]
[Order article via Infotrieve]
43.
Geller RB,
Zahurak M,
Hurwitz CA,
Burke PJ,
Karp JE,
Piantadosi S,
Civin CI:
Prognotic importance of immunophenotyping in adults with acute myelocytic leukemia: The significance of the stem cell glycoprotein CD34 (MY10).
Br J Haematol
76:340,
1990[Medline]
[Order article via Infotrieve]
44.
Jensen A,
Hokland M,
Jorgensen H,
Justesen J,
Ellegaard J,
Hokland P:
Solitary expression of CD7 among T-cell antigens in acute myeloid leukemia: Identification of a group of patients with similar T-cell receptor beta and delta rearrangements and course of disease suggestive of a poor prognosis.
Blood
78:1292,
1991[Abstract/Free Full Text]
45.
Myint H,
Lucie N:
The prognostic significance of the CD34 antigen in acute myeloid leukaemia.
Leuk Lymphoma
7:425,
1992[Medline]
[Order article via Infotrieve]
46.
Cuneo A,
Ferrant A,
Michaux JL,
Boogaerts M,
Demuynck H,
Van Orshoven A,
Criel A,
Stul M,
Cin PD,
Hernandez J,
Chatelain B,
Doyen C,
Louwagie A,
Castoldi G,
Cassiman JJ,
Van Den Berghe H:
Cytogenetic profile of minimally differentiated (FAB M0) acute myeloid leukemia: Correlation with clinicobiologic findings.
Blood
85:3688,
1995[Abstract/Free Full Text]
47.
Hanson CA,
Abaza M,
Sheldon S,
Ross CW,
Schnitzer B,
Stoolman LM:
Acute biphenotypic leukemia: Immunophenotypic and cytogenetic analysis.
Br J Haematol
84:49,
1993[Medline]
[Order article via Infotrieve]
48.
Traweek ST:
Immunophenotypic analysis of acute leukemia.
Am J Clin Pathol
99:504,
1993[Medline]
[Order article via Infotrieve]
49.
Kita K,
Nakase K,
Miwa H,
Masuya M,
Nishii K,
Morita N,
Takakura N,
Otsuji A,
Shirakawa S,
Takanori U,
Nasu K,
Kyo T,
Dohy H,
Kamada N:
Phenotypical characteristics of acute myelocytic leukemia associated with the t(8; 21)(q22; q22) chromosomal abnormality: Frequent expression of immature B-cell antigen CD19 together with stem cell antigen CD34.
Blood
80:470,
1992[Abstract/Free Full Text]
50.
Hurwitz CA,
Raimondi SC,
Head D,
Krance R,
Mirro J Jr,
Kalwinsky DK,
Ayers GD,
Behm FG:
Distinctive immunophenotypic features of t(8; 21) (q22; q22) acute myeloblastic leukemia in children.
Blood
80:3182,
1992[Abstract/Free Full Text]
51.
Swansbury GJ,
Lawler SD,
Alimena G,
Arthur D,
Berger R,
van den Berge H,
Bloomfield CD,
de la Chapelle A,
Dewald G,
Garson OM,
Hagemeijer A,
Mitelman F,
Rowley JD,
Sakurai M:
Long-term survival in acute myelogenous leukemia: A second follow-up of the Fourth International Workshop on Chromosomes in Leukemia.
Cancer Genet Cytogenet
73:1,
1994[Medline]
[Order article via Infotrieve]
52.
Nucifora G,
Rowley JD:
AML1 and the 8; 21 and 3; 21 translocations in acute and chronic myeloid leukemia.
Blood
86:1,
1995[Free Full Text]
53.
Arber DA,
Glackin C,
Lowe G,
Medeiros LJ,
Slovak ML:
Presence of t(8; 21) (q22; q22) in myeloperoxidase-positive, myeloid surface antigen-negative acute myeloid leukemia.
Am J Clin Pathol
107:68,
1997[Medline]
[Order article via Infotrieve]
54.
Frankel SR:
All-trans-retinoic acid in APL.
Contemp Oncol
2:36,
1992
55.
Rovelli A,
Biondi A,
Rajnoldi AC,
Conter V,
Giudici G,
Jankovic M,
Locasciulli A,
Rizzari C,
Romitti L,
Rossi MR,
Schiro R,
Tosi S,
Uderzo C,
Masera G:
Microgranular variant of acute promyelocytic leukemia in children.
J Clin Oncol
10:1413,
1992[Abstract/Free Full Text]
56.
Claxton DF,
Reading CL,
Nagarajan L,
Tsujimoto Y,
Anderson BS,
Estey E,
Cork A,
Huh YO,
Trujillo J,
Deisseroth AB:
Correlation of CD2 expression with PML gene breakpoints in patients with acute promyelocytic leukemia.
Blood
80:582,
1992[Abstract/Free Full Text]
57.
Diverio D,
Lo Coco F,
D'Adamo F,
Biondi A,
Fagioli M,
Grignani F,
Rambaldi A,
Rossi V,
Avvisati G,
Petti MC,
Testi AM,
Liso V,
Specchia G,
Fioritoni G,
Recchia A,
Frassoni F,
Ciolli S,
Pelicci PG,
for the Italian Cooperative Study Group "GIMEMA":
Identification of DNA rearrangements at the retinoic acid receptor- (RAR-) locus in all patients with acute promyelocytic leukemia (APL) and mapping of APL breakpoints within the RAR- second intron.
Blood
79:3331,
1992[Abstract/Free Full Text]
58.
Hiorns LR,
Min T,
Swansbury GJ,
Zelent A,
Dyer MJS,
Catovsky D:
Interstitial insertion of retinoic acid receptor- gene in acute promyelocytic leukemia with normal chromosome 15 and 17.
Blood
83:2946,
1994[Abstract/Free Full Text]
59.
Degos L,
Dombret H,
Chomienne C,
Daniel MT,
Miclea JM,
Chastang C,
Castaigne S,
Fenaux P:
All-trans-retinoic acid as a differentiating agent in the treatment of acute promyelocytic leukemia.
Blood
85:2643,
1995[Free Full Text]
60.
Licht JD,
Chomienne C,
Goy A,
Chen A,
Scott A,
Head D,
Michaux JL,
Wu Y,
DeBlasio A,
Miller WH Jr,
Zelenetz AD,
Willman CL,
Chen Z,
Chen SJ,
Zelent A,
Macintyre E,
Veil A,
Cortes J,
Kantarjian H,
Waxman S:
Clinical and molecular characterization of a rare syndrome of acute promyelocytic leukemia associated with translocation (11; 17).
Blood
85:1083,
1995[Abstract/Free Full Text]
61.
Scott AA,
Head DR,
Kopecky KJ,
Appelbaum FR,
Theil KS,
Grever MR,
Chen I,
Whittaker MH,
Griffith BB,
Licht JD,
Waxman S,
Whalen MM,
Bankhurst AD,
Richter LC,
Grogan TM,
Willman CL:
HLA-DR-, CD33+, CD56+, CD16-, myeloid/natural killer cell acute leukemia: A previously unrecognized form of acute leukemia potentially misdiagnosed as French-American-British acute myeloid leukemia-M3.
Blood
84:244,
1994[Abstract/Free Full Text]
62.
Frankel SR,
Eardley A,
Lauwers G,
Weiss M,
Warrell R:
The "retinoic acid syndrome" in acute promyelocytic leukemia.
Ann Intern Med
117:292,
1992
63.
Warrell RP,
Maslak P,
Eardley A,
Heller G,
Miller WH,
Frankel SR:
Treatment of acute promyelocytic leukemia with all-trans retinoic acid: An update of the New York experience.
Leukemia
8:926,
1994
64.
Vahdat L,
Maslak P,
Miller WH Jr,
Eardley A,
Heller G,
Scheinberg DA,
Warrell RP Jr:
Early mortality and the retinoic acid syndrome in acute promyelocytic leukemia: Impact of leukocytosis, low-dose chemotherapy, PMN/RAR- isoform, and CD13 expression in patients treated with all-trans retinoic acid.
Blood
84:3843,
1994[Abstract/Free Full Text]
65.
Adriaansen HJ,
te Boekhorst PAW,
Hagemeijer AM van der Schoot CE,
Delwel HR,
van Dongen JJM:
Acute myeloid leukemia M4 with bone marrow eosinophilia (m4E0) and inv (16) (p13q22) exhibits a specific immunophenotype with CD2 expression.
Blood
81:3043,
1993[Abstract/Free Full Text]
66.
Paietta E,
Wiernik PH,
Andersen J,
Bennett J,
Yunis J:
Acute myeloid leukemia m4 with inv (16) (p13q22) exhibits a specific immunophenotype with CD2 expression, correspondence.
Blood
82:2595,
1993[Free Full Text]
67.
Larson RA,
Williams SF,
Le Beau MM,
Bitter MA,
Vardiman JW,
Rowley JD:
Acute myelomonocytic leukemia with abnormal eosinophils and inv(16) or t(16; 16) has a favorable prognosis.
Blood
68:1242,
1986[Abstract/Free Full Text]
68.
Haferlach T,
Gassmann W,
Loffler H,
Jurgensen C,
Noak J,
Ludwig WD,
Thiel E,
Haase D,
Fonatsch C,
Becher R,
Schlegelberger B,
Nowrousian MR,
Lengfelder E,
Eimermacher H,
Weh HJ,
Braumann D,
Maschmeyer G,
Koch P,
Heinecke A,
Sauerland MC,
Buchner T,
for the AML Cooperative Group:
Clinical aspects of acute myeloid leukemias of the FAB types M3 and M4Eo.
Ann Hematol
66:165,
1993[Medline]
[Order article via Infotrieve]
69.
Liu PP,
Hajra A,
Wijmenga C,
Collins FS:
Molecular pathogenesis of the chromosome 16 inversion in the M4Eo subtype of acute myeloid leukemia.
Blood
85:2289,
1995[Free Full Text]
70.
Cuneo A,
Van Orshoven A,
Michaux JL,
Boogaerts M,
Louwagie A,
Doyen C,
Dal Cin P,
Fagioli F,
Castoldi G,
Van den Berghe H:
Morphologic, immunologic and cytogenetic studies in erythroleukaemia: Evidence for multilineage involvement and identification of two distinct cytogenetic-clinicopathological types.
Br J Haematol
75:346,
1990[Medline]
[Order article via Infotrieve]
71.
Loken MR,
Shah VO,
Dattilio KL,
Civin CI:
Flow cytometric analysis of human bone marrow: I. Normal erythroid development.
Blood
69:255,
1987[Abstract/Free Full Text]
72.
Betz SA,
Foucar K,
Head DR,
Chen IM,
Willman CL:
False-positive flow cytometric platelet glycoprotein IIb/IIIa expression in myeloid leukemias secondary to platelet adherence to blasts.
Blood
79:2399,
1992[Abstract/Free Full Text]
73.
Ivanyi JL,
Kiss A,
Telek B,
Tornai I:
Megakaryocyte markers in myeloproliferative disorders.
Acta Histochem
95:79,
1993[Medline]
[Order article via Infotrieve]
74.
Matolcsy A,
Kalman E,
Pajor L,
Konya T,
Weber E:
Morphologic and flow cytometric analysis of circulating megakaryoblasts in chronic myeloid leukameia.
Leuk Res
15:887,
1991[Medline]
[Order article via Infotrieve]
75.
Dercksen MW,
Weimar IS,
Rihel DJ,
Breton-Gorius J,
Vainchenker W,
Slaper-Cortenbach ICM,
Pinedo HM,
von dem Borne AEGKr,
Gerritsen WR,
van der Schoot CE:
The value of flow cytometric analysis of platelet glycoprotein expression on CD34+ cells measured under conditions that prevent p-selectin-mediated binding of platelets.
Blood
86:3771,
1995[Abstract/Free Full Text]
76.
Byrd JC,
Edenfield WJ,
Shields DJ,
Dawson NA:
Extramedullary myeloid cell tumors in acute nonlymphocytic leukemia: A clinical review.
J Clin Oncol
13:1800,
1995[Abstract/Free Full Text]
77.
Imrie KR,
Kovacs MJ,
Selby D,
Lipton J,
Patterson BJ,
Pantalony D,
Poldre P,
Ngan BY,
Keating A:
Isolated chloroma: The effect of early antileukemic therapy.
Ann Intern Med
123:351,
1995[Abstract/Free Full Text]
78.
Tallman MS,
Hakimian D,
Shaw JM,
Lissner GS,
Russell EJ,
Variakojis D:
Granulocytic sarcoma is associated with the 8; 21 translocation in acute myeloid leukemia.
J Clin Oncol
11:690,
1993[Abstract]
79.
Uckun FM,
Sather H,
Reaman G,
Shuster J,
Land V,
Trigg M,
Gunther R,
Chelstrom L,
Bleyer A,
Gaynon P,
Crist W:
Leukemic cell growth in SCID mice as a predictor of relapse in high-risk B-lineage acute lymphoblastic leukemia.
Blood
85:873,
1995[Abstract/Free Full Text]
80.
Ong ST,
Larson RA:
Current management of acute lymphoblastic leukemia in adults.
Oncology
9:433,
1995[Medline]
[Order article via Infotrieve]
81.
Copelan EA,
McGuire EA:
The biology and treatment of acute lymphoblastic leukemia in adults.
Blood
85:1151,
1995[Abstract/Free Full Text]
82.
Kantarjian HM:
Adult acute lymphoblastic leukemia: Critical review of current knowledge.
Am J Med
97:176,
1994[Medline]
[Order article via Infotrieve]
83.
Pui CH,
Behm FG,
Crist WM:
Clinical and biologic relevance of immunologic marker studies in childhood acute lymphoblastic leukemia.
Blood
82:343,
1993[Abstract/Free Full Text]
84.
Crist W,
Shuster J,
Look T,
Borowitz M,
Behm F,
Bowman P,
Frankel L,
Pullen J,
Krance R,
Steuber P,
Camitta B,
Amylon M,
Link M,
Land V:
Current results of studies of immunophenotype-, age- and leukocyte-based therapy for children with acute lymphoblastic leukemia.
Leukemia
6:162,
1992
85.
Pui C-H:
Childhood leukemias.
N Engl J Med
332:1618,
1995[Free Full Text]
86.
Trueworthy R,
Shuster J,
Look T,
Crist W,
Borowitz M,
Carroll A,
Frankel L,
Harris M,
Wagner H,
Haggard M,
Mosijczuk A,
Pullen J,
Steuber P,
Land V:
Ploidy of lymphocytes is the strongest predictor of treatment outcome in B-progenitor cell acute lymphoblastic leukemia of childhood: A Pediatric Oncology Group study.
J Clin Oncol
10:606,
1992[Abstract/Free Full Text]
87.
Pui C-H,
Carroll AJ,
Raimondi SC,
Land VJ,
Crist WM,
Shuster JJ,
Williams DL,
Pullen DJ,
Borowitz MJ,
Behm FG:
Clinical presentation, karyotypic characterization, and treatment outcome of childhood acute lymphoblastic leukemia with a near-haploid or hypodiploid less than 45 line.
Blood
75:1170,
1990[Abstract/Free Full Text]
88.
Pui C-H,
Williams DL,
Raimondi SC,
Melvin SL,
Behm FG,
Look AT,
Dahl GV,
Rivera GK,
Kalwinsky DK,
Mirro J,
Dodge RK,
Murphy SB:
Unfavorable presenting clinical and laboratory features are associated with CALLA-negative non-T, non-B lymphoblastic leukemia in children.
Leuk Res
11:1287,
1986
89.
Pui C-H,
Rivera GK,
Hancock ML,
Raimondi SC,
Sandlund JT,
Mahmoud HH,
Ribeiro RC,
Furman WL,
Hurwitz CA,
Crist WM,
Behm FG:
Clinical significance of CD10 expression in childhood acute lymphoblastic leukemia.
Leukemia
7:35,
1993[Medline]
[Order article via Infotrieve]
90. Tritz D, Pettigrew A, Talkington S, Smith L, Jennings CD: Association of CD-15 expression and 11q23 translocation in acute leukemias. Mod Pathol 8:122A, 1995
91.
Bloomfield CD,
Secker-Walker LM,
Goldman AI,
Van Den Berge H,
de la Chapelle A,
Ruutu T,
Alimena G,
Garson OM,
Golomb HM,
Rowley JD:
Sixth international workshop on chromosomes and leukemias: Six-year follow-up of the clinical significance of karyotype in acute lymphoblastic leukemia.
Cancer Genet Cytogenet
40:171,
1989[Medline]
[Order article via Infotrieve]
92.
Morgan GJ,
Shiach C,
Potter M:
The clinical value of detecting gene rearrangements in acute leukemias.
Br J Haematol
88:459,
1994[Medline]
[Order article via Infotrieve]
93.
Lu D,
Liu J,
Campbell M,
Guo JQ,
Heisterkamp N,
Groffen J,
Canaai E,
Arlinghaus R:
Tyrosine phosphorylation of P160 BCR by P210 BCR-ABL.
Blood
82:1257,
1993[Abstract/Free Full Text]
94.
Pendergast AM,
Muller AJ,
Havlik MH,
Maru Y,
Witte ON:
BCR sequences essential for transformation by the BCR-ABL oncogene bind to the ABL SH2 regulatory domain in a non-phosphotyrosine-dependent manner.
Cell
66:161,
1991[Medline]
[Order article via Infotrieve]
95.
Diekmann D,
Brill S,
Garrett MD,
Totty N,
Hsuan J,
Monfries C,
Hall C,
Lim L,
Hall A:
BCR encodes a GTPase-activating protein for p21rac.
Nature
351:400,
1991[Medline]
[Order article via Infotrieve]
96.
Westbrook CA,
Hooberman AL,
Spino C,
Dodge RK,
Larson RA,
Davey F,
Wurster-Hill DH,
Sobol RE,
Schiffer C,
Bloomfield CD:
Clinical significance of the BCR-ABL fusion gene in adult acute lymphoblastic leukemia: A Cancer and Leukemia Group B Study (8762).
Blood
80:2983,
1992[Abstract/Free Full Text]
97.
Crist WM,
Carroll AJ,
Shuster JJ,
Jackson J,
Head DR,
Borowitz MJ,
Behm FG,
Link M,
Steuber CP,
Ragab A,
Hirt A,
Brock B,
Land V,
Pullen DJ:
Philadelphia chromosome positive childhood acute lymphoblastic leukemia: Clinical and cytogenetic characteristics and treatment outcome. A Pediatric Oncology Group study.
Blood
76:489,
1990[Abstract/Free Full Text]
98.
Preti HA,
O'Brien S,
Giralt S,
Beran M,
Pierce S,
Kantarjian HM:
Philadelphia-chromosome-positive adult acute lymphocytic leukemia: Characteristics, treatment results, and prognosis in 41 patients.
Am J Med
97:60,
1994[Medline]
[Order article via Infotrieve]
99.
Larson RA,
Dodge RK,
Burns CP,
Lee EJ,
Stone RM,
Schulman P,
Duggan D,
Davey FR,
Sobol RE,
Frankel SR,
Hooberman AL,
Westbrook CA,
Arthur DC,
George SL,
Bloomfield CD,
Schiffer CA:
A five-drug remission induction regimen with intensive consolidation for adults with acute lymphoblastic leukemia: Cancer and leukemia group B study 8811.
Blood
85:2025,
1995[Abstract/Free Full Text]
100.
Pui C-H:
Acute leukemias with the t(4; 11)(q21; q23).
Leuk Lymphoma
7:173,
1992[Medline]
[Order article via Infotrieve]
101.
Chen C-S,
Sorensen PHB,
Domer PH,
Reaman GH,
Korsmeyer SJ,
Heerema NA,
Hammond GD,
Kersey JH:
Molecular rearrangements on chromosome 11q23 predominate in infant acute lymphoblastic leukemia and are associated with specific biologic variables and poor outcome.
Blood
81:2386,
1993[Abstract/Free Full Text]
102.
Pui C-H,
Crist WM,
Look AT:
Biology and clinical significance of cytogenetic abnormalities in childhood acute lymphoblastic leukemia.
Blood
76:1449,
1990[Abstract/Free Full Text]
103.
Pui C-H,
Raimondi SC,
Head DR,
Schell MJ,
Rivera GK,
Mirro J,
Crist WM,
Behm FG:
Characterization of childhood acute leukemia with multiple myeloid and lymphoid markers at diagnosis and at relapse.
Blood
78:1327,
1991[Abstract/Free Full Text]
104.
Pui C-H,
Frankel LS,
Carroll AJ,
Raimondi SC,
Shuster JJ,
Head DR,
Crist WM,
Land VJ,
Pullen DJ,
Steuber CP,
Behm FG,
Borowitz MJ:
Clinical characteristics and treatment outcome of childhood acute lymphoblastic leukemia with the t(4; 11)(q21; q23): A collaborative study of 40 cases.
Blood
77:440,
1991[Abstract/Free Full Text]
105.
Boucheix C,
David B,
Sebban C,
Racadot E,
Bene M-C,
Bernard A,
Campos L,
Jouault H,
Sigaux F,
Lepage E,
Herve P,
Fiere D for the French Group on Therapy for Adult Lymphoblastic Leukemia:
Immunophenotype of adult acute lymphoblastic leukemia, clinical parameters, and outcome: An analysis of a prospective trial including 562 tested patients (LALA87).
Blood
84:1603,
1994[Abstract/Free Full Text]
106.
Okuda T,
Fisher R,
Downing JR:
Molecular diagnostics in pediatric acute lymphoblastic leukemia.
Mol Diagnosis
1:139,
1996[Medline]
[Order article via Infotrieve]
107.
Romana SP,
Poirel H,
Leconiat M,
Flexor MA,
Mauchauffe M,
Jonveaux P,
Macintyre EA,
Berger R,
Bernard OA:
High frequency of t(12; 21) in childhood B-lineage acute lymphoblastic leukemia.
Blood
86:4263,
1995[Abstract/Free Full Text]
108.
Shurtleff SA,
Buijs A,
Behm FG,
Rubnitz JE,
Raimondi SC,
Hancock ML,
Chan GC-F,
Pui C-H,
Grosveld G,
Downing JR:
TEL/AML1 fusion resulting from a cryptic t(12; 21) is the most common genetic lesion in pediatric ALL and defines a subgroup of patients with an excellent prognosis.
Leukemia
9:1985,
1995[Medline]
[Order article via Infotrieve]
109.
Liang CD,
Chou TB,
Chen JS,
Shurtleff SA,
Rubnitz JE,
Downing JR,
Pui CH,
Shih LY:
High incidence if TEL/AML1 fusion resulting from a cryptic t(12; 21) in childhood B-lineage acute lymphoblastic leukemia in Taiwan.
Leukemia
10:991,
1996[Medline]
[Order article via Infotrieve]
110.
Leitenberg D,
Rappeport JM,
Smith BR:
B-cell precursor bone marrow reconstitution after bone marrow transplantation.
Am J Clin Pathol
102:231,
1994[Medline]
[Order article via Infotrieve]
111.
Davis RE,
Longacre TA,
Cornbleet PJ:
Hematogones in the bone marrow of adults. Immunophenotypic features, clinical settings, and differential diagnosis.
Am J Clin Pathol
102:202,
1994[Medline]
[Order article via Infotrieve]
112.
Richard G,
Brody J,
Sun T:
A case of acute megakaryocytic leukemia with hematogones.
Leukemia
7:1900,
1993[Medline]
[Order article via Infotrieve]
113.
Hurwitz CA,
Gore SD,
Stone KD,
Civin CI:
Flow cytometric detection of rare normal human marrow cells with immunophenotypes characteristic of acute lymphoblastic leukemia cells.
Leukemia
6:233,
1992[Medline]
[Order article via Infotrieve]
114.
Farahat N,
Lens D,
Zomas A,
Morilla R,
Matutes E,
Catovsky D:
Quantitative flow cytometry can distinguish between normal and leukemic B-cell precursors.
Br J Haematol
91:640,
1995[Medline]
[Order article via Infotrieve]
115.
Pui C-H,
Williams DL,
Roberson PK,
Raimondi SC,
Behm FG,
Lewis SH,
Rivera GK,
Kalwinsky DK,
Abromowitch M,
Crist WM,
Murphy SB:
Correlation of karyotype and immunophenotype in childhood acute lymphoblastic leukemia.
J Clin Oncol
6:56,
1988[Abstract]
116.
Crist W,
Boyett J,
Roper M,
Pullen J,
Metzgar R,
van Eys J,
Ragab A,
Starling K,
Vietti T,
Cooper M:
Pre-B cell leukemia responds poorly to treatment: A Pediatric Oncology Group study.
Blood
63:407,
1984[Abstract/Free Full Text]
117.
Crist W,
Boyett J,
Jackson J,
Vietta T,
Borowitz M,
Chauvenet A,
Winick N,
Ragab A,
Mahoney D,
Head D,
Iyer R,
Wagner H,
Pullen J:
Prognostic importance of the pre-B-cell immunophenotype and other presenting features in B-lineage childhood acute lymphoblastic leukemia: A Pediatric Oncology Group study.
Blood
74:1252,
1989[Abstract/Free Full Text]
118.
Raimondi SC,
Behm FG,
Roberson PK,
Williams DL,
Pui C-H,
Crist WM,
Look AT,
Rivera GK:
Cytogenetics of pre-B-cell acute lymphoblastic leukemia with emphasis on prognostic implications of the t(1; 19).
J Clin Oncol
8:1380,
1990[Abstract]
119.
Crist WM,
Carroll AJ,
Shuster JJ,
Behm FG,
Whitehead M,
Vietti TJ,
Look AT,
Mahoney D,
Ragab A,
Pullen DJ,
Land VJ:
Poor prognosis of children with pre-B acute lymphoblastic leukemia is associated with the t(1; 19)(q23; p13): A Pediatric Oncology Group study.
Blood
76:117,
1990[Abstract/Free Full Text]
120.
Borowitz MJ,
Hunger SP,
Carroll AJ,
Shuster JJ,
Pullen DJ,
Steuber CP,
Cleary ML:
Predictability of the t(1; 19)(q23; p13) from surface antigen phenotype: Implications for screening cases of childhood acute lymphoblastic leukemia for molecular analysis: A Pediatric Oncology Group study.
Blood
82:1086,
1993[Abstract/Free Full Text]
121.
Pui C-H,
Hancock ML,
Head DR,
Rivera GK,
Look AT,
Sandlund JT,
Behm FG:
Clinical significance of CD34 expression in childhood acute lymphoblastic leukemia.
Blood
82:889,
1993[Abstract/Free Full Text]
122.
Soussain C,
Patte C,
Ostronoff M,
Delmer A,
Rigal-Huguet F,
Cambier N,
Leprise P-Y,
Francois S,
Cony-Makhoul P,
Harousseau JL,
Janvier M,
Chauvenet L,
Witz F,
Pico J:
Small noncleaved cell lymphoma and leukemia in adults. A retrospective study of 65 adults treated with the LMB pediatric protocols.
Blood
85:664,
1995[Abstract/Free Full Text]
123.
Cortes J,
O'Brien SM,
Pierce S,
Keating MJ,
Freireich EJ,
Kantarjian HM:
The value of high-dose systemic chemotherapy and intrathecal therapy for central nervous system prophylaxis in different risk groups of adult acute lymphoblastic leukemia.
Blood
86:2091,
1995[Abstract/Free Full Text]
124.
Hammami A,
Chan WC,
Michels SD,
Nassar VH:
Mature B-cell acute leukemia: A clinical, morphological, immunological, and cytogenetic study of nine cases.
Hematol Pathol
5:109,
1991[Medline]
[Order article via Infotrieve]
125.
Rowe D,
Devaraj PE,
Irving JAE,
Hogarth L,
Hall AG,
Turner GE:
A case of mature B-cell ALL with coexistence of t(1; 19) and t(14; 18) and expression of the E2A/PBX1 fusion gene.
Br J Haematol
94:133,
1996[Medline]
[Order article via Infotrieve]
126.
Kouides PA,
Phatak PD,
Wang N,
Bennett JM:
B-cell acute lymphoblastic leukemia with L1 morphology and coexistence of t(1; 19) and t(14; 18) chromosome translocations.
Cancer Genet Cytogenet
78:23,
1994[Medline]
[Order article via Infotrieve]
127.
Thiel E,
Kranz BR,
Raghavachar A,
Bartram CR,
Loffler H,
Messerer D,
Ganser A,
Ludwig W-D,
Buchner T,
Hoelzer D:
Prethymic phenotype and genotype of pre-T (CD7+/ER-)-cell leukemia and its clinical significance within adult acute lymphoblastic leukemia.
Blood
73:1247,
1989[Abstract/Free Full Text]
128.
Shuster JJ,
Falletta JM,
Pullen DJ,
Crist WM,
Humphrey GB,
Dowell BL,
Wharam MD,
Borowitz M:
Prognostic factors in childhood T-cell acute lymphoblastic leukemia: A Pediatric Oncology Group study.
Blood
75:166,
1990[Abstract/Free Full Text]
129.
Pui C-H,
Behm GF,
Singh B,
Schell MJ,
Williams DL,
Rivera GK,
Kalwinsky DK,
Sandlund JT,
Crist WM,
Raimondi SC:
Heterogeneity of presenting features and their relation to treatment outcome in 120 children with T-cell acute lymphoblastic leukemia.
Blood
75:174,
1990[Abstract/Free Full Text]
130.
Inhorn RC,
Aster JC,
Roach SA,
Slapak CA,
Soiffer R,
Tantravahi R,
Stone RM:
A syndrome of lymphoblastic lymphoma, eosinophilia, and myeloid hyperplasia/malignancy with t(8; 13) (p11; q11): Description of a distinctive clinicopathologic entity.
Blood
85:1881,
1995[Abstract/Free Full Text]
131.
Abruzzo LV,
Jaffe ES,
Cotelingam JD,
Whang-Peng J,
Del Duca V,
Medeiros LJ:
T-Cell lymphoblastic lymphoma with eosinophils associated with subsequent myeloid malignancy.
Am J Surg Pathol
16:236,
1992[Medline]
[Order article via Infotrieve]
132.
Campana D,
Hansen-Hagge T,
Matutes E,
Coustan-Smith E,
Yokota S,
Shetty V,
Bartram C,
Janossy G:
Phenotypic, genotypic, cytochemical, and ultrastuctural characterization of acute undifferentiated leukemia.
Leukemia
4:620,
1990[Medline]
[Order article via Infotrieve]
133.
Drach D,
Drach J,
Glassl H,
Gattringer C,
Huber H:
Flow cytometric detection of cytoplasmic antigens in acute leukemias: implications for lineage assignment.
Leuk Res
17:455,
1993[Medline]
[Order article via Infotrieve]
134.
Howell AL,
Stukel TA,
Bloomfield CD,
Ball ED:
Predictive value of flow cytometric analyses of blast cells in assessing the phenotype of the leukemia colony-forming cell (L-CFC) population in acute myeloid leukemia.
Bone Marrow Transplant
10:261,
1992[Medline]
[Order article via Infotrieve]
135.
Jowitt SN,
Yin JAL,
Saunders MJ:
Relapsed myelodysplastic clone differs from acute onset clone as shown by X-linked DNA polymorphism in a patient with acute myeloid leukemia.
Blood
82:613,
1993[Abstract/Free Full Text]
136.
Bernstein ID,
Singer JW,
Smith FO,
Andrews RG,
Flowers DA,
Petersens J,
Steinmann L,
Najfeld V,
Savage D,
Fruchtman S,
Arlin Z,
Fialkow PJ:
Differences in the frequency of normal and clonal precursors of colony-forming cells in chronic myelogenous leukemia and acute myelogenous leukemia.
Blood
79:1811,
1992[Abstract/Free Full Text]
137.
Macedo A,
Orfao A,
Gonzalez M,
Vidriales MB,
Lopez-Berges MC,
martinez A,
San Miguel JF:
Immunological detection of blast cell subpopulations in acute myeloblastic leukemia at diagnosis: Implications for minimal residual disease studies.
Leukemia
9:993,
1995[Medline]
[Order article via Infotrieve]
138.
Buccheri V,
Matutes E,
Dyer MJS,
Catovsky D:
Lineage commitment in biphenotypic acute leukemia.
Leukemia
7:919,
1993[Medline]
[Order article via Infotrieve]
139.
Saikevych IA,
Kerrigan DP,
McConnell TS,
Head DR,
Appelbaum FR,
Willman CL:
Multparameter analysis of acute mixed lineage leukemia: Correlation of a B/myeloid immunophenotype and immunoglobulin and T-cell receptor gene rearrangements with the presence of the Philadelphia chromosome translocation in acute leukemias with myeloid morphology.
Leukemia
5:373,
1991[Medline]
[Order article via Infotrieve]
140.
Hayashi Y,
Sugta K,
Nakazawa S,
Abe T,
Kojima S,
Inaba T,
Hanada R,
Tamamoto K:
Karyotypic patterns in acute mixed lineage leukemia.
Leukemia
4:121,
1990[Medline]
[Order article via Infotrieve]
141.
Shipp MA,
Look AT:
Hematopoietic differentiation antigens that are membrane-associated enzymes: Cutting is the key!
Blood
82:1052,
1993[Free Full Text]
142.
Fialkow PJ,
Jacobson RJ,
Papayannopoulou T:
Chronic myelocytic leukemia. Clonal origin in a stem cell common to the granulocyte, erythrocyte, platelet, and monocyte/macrophage.
Am J Med
63:125,
1977[Medline]
[Order article via Infotrieve]
143.
Greenberg BR,
Wilson FD,
Woo L,
Jenks HM:
Cytogenetic of fibroblastic colonies in Ph1-positive chronic myelogenous leukemia.
Blood
51:1039,
1978[Abstract/Free Full Text]
144.
Nowell PC,
Hungerford DA:
A minute chromosome in human chronic granulocytic leukemia.
Science
132:1497,
1960
145.
Rowley JD:
A new consistent chromosomal abnormality in chronic myelogenous leukemia identified by quinacrine fluorescence and Giemsa staining.
Nature
243:290,
1973[Medline]
[Order article via Infotrieve]
146.
Daley GQ,
Van Etten RA,
Baltimore D:
Induction of chronic myelogenous leukemia in mice by the P210 bcr/abl gene of the Philadelphia chromosome.
Science
247:824,
1990[Abstract/Free Full Text]
147.
Testoni N,
Martinelli G,
Farabegoli P,
Zaccaria A,
Amabile M,
Raspadori D,
Pelliconi S,
Zuffa E,
Carboni C,
Tura S:
A new method of "in-cell reverse transcriptase-polymerase chain reaction" for the detection of BCR/ABL transcript in chronic myeloid leukemia patients.
Blood
87:3822,
1996[Abstract/Free Full Text]
148.
Kantarjian HM,
Deisseroth A,
Kurzrock R,
Estrov Z,
Talpaz M:
Chronic myelogenous leukemia: A concise update.
Blood
82:691,
1993[Free Full Text]
149.
Wetzler M,
Kantarjian H,
Kurzrock R,
Talpaz M:
Interferon- therapy for chronic myelogenous leukemia.
Am J Med
99:402,
1995[Medline]
[Order article via Infotrieve]
150.
McGlave P,
Bartsch G,
Anasetti C,
Ash R,
Beatty P,
Gajewski J,
Kernan NA:
Unrelated donor marrow transplantation therapy for chronic myelogenous leukemia: Initial experience of the national marrow donor program.
Blood
81:543,
1993[Abstract/Free Full Text]
151.
Derderian PM,
Kantarjian HM,
Talpaz M,
O'Brien S,
Cork A,
Estey E,
Pierce S,
Keating M:
Chronic myelogenous leukemia in the lymphoid blastic phase: Characteristics, treatment response and prognosis.
Am J Med
94:69,
1993[Medline]
[Order article via Infotrieve]
152.
Fermand JP,
Sigaux F,
Tsapis A,
Mathieu-Mahul D,
Schmitt C,
Daniel MT,
Seligmann M,
Berger R,
Brouet JC:
T cell-derived blast crisis in chronic myelocytic leukemia.
Leukemia
1:210,
1987[Medline]
[Order article via Infotrieve]
153.
Allouche M,
Bourinbaiar A,
Georgoulias V,
Consolini R,
Salvatore A,
Auclair H,
Jasmin C:
T cell lineage involvement in lymphoid blast crisis of chronic myeloid leukemia.
Blood
66:115,
1985[Abstract/Free Full Text]
154.
Griffin JD,
Tantravahi R,
Canellos GP,
Wisch JS,
Reinherz EL,
Sherwood G,
Beveridge RP,
Daley JF,
Lane H,
Schlossman SF:
T-cell surface antigens in a patient with blast crisis of chronic myeloid leukemia.
Blood
61:640,
1983[Abstract/Free Full Text]
155.
Verfaillie CM,
Miller WJ,
Boylan K,
McGlave PB:
Selection of benign primitive hematopoietic progenitors in chronic myelogenous leukemia on the basis of HLA-DR antigen expression.
Blood
79:1003,
1992[Abstract/Free Full Text]
156.
Turham AJ,
Humphries RK,
Eaves CJ,
Barnett MJ,
Phillips GL,
Kalousek DK,
Klingeman HG,
Lansdorp PL,
Reece DE,
Shephard JD,
Eaves CA:
Detection of breakpoint cluster region-negative and non- clonal hematopoiesis in vitro and in vivo after transplantation of cells selected in cultures of chronic myeloid leukemia marrow.
Blood
76:2404,
1990[Abstract/Free Full Text]
157.
Barnett MJ,
Eaves CJ,
Phillips GL,
Gascoyne RD,
Hogge DE,
Horsman DE,
Humphries RK,
Klingemann H-G,
Lansdorp PM,
Nantel SH,
Reece DE,
Shepherd JD,
Spinelli JJ,
Sutherland HJ,
Eaves AC:
Autografting with cultured marrow in chronic myeloid leukemia: Results of a pilot study.
Blood
84:724,
1994[Abstract/Free Full Text]
158.
Foon KA,
Rai KR,
Gale RP:
Chronic lymphocytic leukemia: New insights into biology and therapy.
Ann Intern Med
113:525,
1990
159.
O'Brien S,
del Giglio A,
Keating M:
Advances in the biology and treatment of B-cell chronic lymphocytic leukemia.
Blood
85:307,
1995[Abstract/Free Full Text]
160.
Rozman C,
Montserrat E:
Chronic lymphocytic leukemia.
N Engl J Med
333:1052,
1995[Free Full Text]
161.
Montserrat E,
Rozman C:
Chronic lymphocytic leukaemia treatment.
Blood Rev
7:164,
1993[Medline]
[Order article via Infotrieve]
162.
Faguet GB:
Chronic lymphocytic leukemia: An updated review.
J Clin Oncol
12:1974,
1994[Abstract/Free Full Text]
163.
Montserrat E,
Binet JL,
Catovsky D,
Dighiero G,
Gale RP,
Rai KR,
Rozman C:
5th International Workshop on Chronic Lymphocytic Leukemia.
Leuk Res
16:717,
1992[Medline]
[Order article via Infotrieve]
164.
Harris NL,
Jaffe ES,
Stein H,
Banks PM,
Chan JKC,
Cleary ML,
Delsol G,
De Wolf-Peeters C,
Brunangelo F,
Gatter KC,
Grogan TM,
Isaacson PG,
Knowles DM,
Mason DY,
Muller-Hermelink HK,
Pileri SA,
Piris MA,
Ralfkiaer Warnke RA:
A revised European-American classification of lymphoid neoplasms: A proposal from the International Lymphoma Study Group.
Blood
84:1361,
1994[Free Full Text]
165.
Que TH,
Marco JG,
Ellis J,
Matutes E,
Babapulle VB,
Boyle S,
Catovsky D:
Trisomy 12 in chronic lymphocytic leukemia detected by fluorescence in situ hybridization: Analysis by stage, immunophenotype and morphology.
Blood
82:571,
1993[Abstract/Free Full Text]
166.
Dorfman DM,
Pinkus GS:
Distinction between small lymphocytic and mantle cell lymphoma by immunoreactivity for CD23.
Mod Pathol
7:326,
1994[Medline]
[Order article via Infotrieve]
167.
Robbins BA,
Ellison DJ,
Spinosa JC,
Carey CA,
Lukes RJ,
Poppema S,
Saven A,
Piro LD:
Diagnostic application of two-color flow cytometry in 161 cases of hairy cell leukemia.
Blood
82:1277,
1993[Abstract/Free Full Text]
168.
Almasri NM,
Duque RE,
Iturraspe J,
Everett E,
Braylan RC:
Reduced expression of CD20 antigen as a characteristic marker for chronic lymphocytic leukemia.
Am J Hematol
40:259,
1992[Medline]
[Order article via Infotrieve]
169.
Finn WG,
Thangavelu M,
Yelavarthi KK,
Goolsby CL,
Tallman MS,
Traynor A,
Peterson LC:
Karyotype correlates with peripheral blood morphology and immunophenotype in chronic lymphocytic leukemia.
Am J Clin Pathol
105:458,
1996[Medline]
[Order article via Infotrieve]
170.
Matutes E,
Oscier D,
Garcia-Marco J,
Ellis J,
Copplestone A,
Gillingham R,
Hamblin T,
Lens D,
Swansbury GJ,
Catovsky D:
Trisomy 12 defines a group of CLL with atypical morphology: Correlation between cytogenetic, clinical and laboratory features in 544 patients.
Br J Haematol
92:382,
1996[Medline]
[Order article via Infotrieve]
171.
Batata A,
Shen B:
Immunophenotyping of subtypes of B-chronic (mature) lymphoid leukemia. A study of 242 cases.
Cancer
70:2436,
1992[Medline]
[Order article via Infotrieve]
172.
Foon KA,
Thiruvengadam R,
Saven A,
Bernstein ZP,
Gale RP:
Genetic relatedness of lymphoid malignancies: Transformation of chronic lymphomytic leukemia as a model.
Ann Intern Med
119:63,
1993[Abstract/Free Full Text]
173.
Villalona-Calero M,
Stewart C,
Barcos M,
Baiocchi R,
Caligiuri M,
Foon KA:
Phenotypic characteristics of "prolymphocytoid" transformed (CLL/PLL) chronic lymphocytic leukemia (CLL) cells.
Proc Am Soc Clin Oncol
10:230,
1991
174.
Banks PM,
Chan J,
Cleary ML,
Delsol G,
De Wolf-Peeters C,
Gatter K,
Grogan TM,
Harris NL,
Isaacson PG,
Jaffe ES,
Mason D,
Pileri S,
Ralfkiaer E,
Stein H,
Warnke RA:
Mantle cell lymphoma: A proposal for unification of morphologic, immunologic, and molecular data.
Am J Surg Pathol
16:637,
1992[Medline]
[Order article via Infotrieve]
175.
Geisler CH,
Larsen JK,
Hansen NE,
Hansen MM,
Christensen BE,
Lund B,
Nielsen H,
Plesner T,
Thorling K,
Andersen E:
Prognostic importance of flow cytometric immunophenotyping of 540 consecutive patients with B-cell chronic lymphocytic leukemia.
Blood
78:1795,
1991[Abstract/Free Full Text]
176.
Salomon-Nguyen F,
Valensie F,
Merle-Beral H,
Flandrin G:
A scoring system for the classification of CD5-B CLL versus CD5+ B CLL and B PLL.
Leuk Lymphoma
16:445,
1995[Medline]
[Order article via Infotrieve]
177.
Maloum K,
Davi F,
Magnac C,
Pritsch O,
McIntyre E,
Valensi F,
Binet JL,
Merle-Beral H,
Dighiero G:
Analysis of VH gene expression in CD5+ and CD5- B-cell chronic lymphocytic leukemia.
Blood
86:3883,
1995[Abstract/Free Full Text]
178.
Kipps TJ,
Carson DA:
Autoantibodies in chronic lymphocytic leukemia and related systemic autoimmune diseases.
Blood
81:2475,
1993[Free Full Text]
179.
Ikematsu W,
Ikematsu H,
Okamura S,
Otsuka T,
Harada M,
Niho Y:
Surface phenotype and Ig heavy-chain gene usage in chronic B-cell leukemias: Expression of myelomonocytic surface markers in CD5- chronic B-cell leukemia.
Blood
83:2602,
1994[Abstract/Free Full Text]
180.
Huang JC,
Finn WG,
Variakojis D,
Goolsby CL,
Peterson LC:
CD5 negative (-) chronic B cell leukemias are rarely classifiable as B cell chronic lymphocytic leukemia (B-CLL).
Mod Pathol
10:127a,
1997
181.
Huh YO,
Pugh WC,
Kantarjian HM,
Stass SA,
Cork A,
Trujillo JM,
Keating MJ:
Detection of subgroups of chronic B-cell leukemias by FMC7 monoclonal antibody.
Am J Clin Pathol
101:283,
1994[Medline]
[Order article via Infotrieve]
182.
Zukerburg LR,
Medeiros LJ,
Ferry JA,
Harris NL:
Diffuse low-grade B-cell lymphomas: Four clinically distinct subtypes defined by a combination of morphologic and immunophenotypic features.
Am J Clin Pathol
100:373,
1993[Medline]
[Order article via Infotrieve]
183.
Hanada M,
Delia D,
Aiello A,
Stadtmauer E,
Reed J:
bcl-2 gene hypomethylation and high-level expression in B-cell chronic lymphocytic leukemia.
Blood
82:1820,
1993[Abstract/Free Full Text]
184.
Schena M,
Larsson LG,
Gottardi D,
Gaidano G,
Carlsson M,
Nilsson K,
Caligaris-Cappio F:
Growth- and differentiation-associated expression of bcl-2 in B-chronic lymphocytic leukemia cells.
Blood
79:2981,
1992[Abstract/Free Full Text]
185.
Matolcsy A,
Inghirami G,
Knowles DM:
Molecular genetic demonstration of the diverse evolution of Richter's syndrome (chronic lymphocytic leukemia and subsequent large cell lymphoma).
Blood
83:1363,
1994[Abstract/Free Full Text]
186.
Robertson LE,
Huh YO,
Butler JJ,
Pugh WC,
Hirsch-Ginsberg C,
Stass S,
Kantarjian H,
Keating MJ:
Response assessment in chronic lymphocytic leukemia after fludarabine plus prednisone: Clinical, pathologic immunophenotypic, and molecular analysis.
Blood
80:29,
1992[Abstract/Free Full Text]
187.
Vuillier F,
Claisse JF,
Vandenvelde C,
Travade P,
Magnac C,
Chevret S,
Desablens B,
Binet JL,
Dighiero G:
Evaluation of residual disease in B-cell chronic lymphocytic leukemia patients in clinical and bone-marrow remission using CD5-CD19 markers and PCR study of gene rearrangements.
Leuk Lymphoma
7:195,
1992[Medline]
[Order article via Infotrieve]
188.
Cousar JB:
Surgical pathology examination of lymph nodes.
Am J Clin Pathol
104:126,
1995[Medline]
[Order article via Infotrieve]
189.
Tbakhi A,
Edinger M,
Myles J,
Pohlman B,
Tubbs RR:
Flow cytometric immunophenotyping of non-Hodgkin's lymphomas and related disorders.
Cytometry
25:113,
1996[Medline]
[Order article via Infotrieve]
190.
McCoy JP Jr,
Overton WR:
A survey of current practices in clinical flow cytometry.
Am J Clin Pathol
106:82,
1996[Medline]
[Order article via Infotrieve]
191.
Robins DB,
Katz RL,
Swan F Jr,
Atkinson EN,
Ordonez NG,
Huh YO:
Immunotyping of lymphoma by fine-needle aspiration: A comparative study of cytospin preparations and flow cytometry.
Am J Clin Pathol
101:569,
1994[Medline]
[Order article via Infotrieve]
192.
Hanson CA:
Fine-needle aspiration and immunophenotyping: A role in diagnostic hematopathology?
Am J Clin Pathol
101:555,
1994[Medline]
[Order article via Infotrieve]
193.
Macartney JC,
Camplejohn RS:
DNA flow cytometry of non-Hodgkin's lymphomas.
Eur J Cancer
26:635,
1990
194.
Rehn S,
Glimelius B,
Strang P,
Sundstrom C,
Tribukait B:
Prognostic significance of flow cytometry studies in B-cell non-Hodgkin lymphoma.
Hematol Oncol
8:1,
1990[Medline]
[Order article via Infotrieve]
195.
Brons PPT,
Raemaekers JMM,
Bogman MJJT,
van Erp PEJ,
Boezeman JBM,
Pennings AHM,
Wessels HMC,
Haanen C:
Cell cycle kinetics in malignant lymphoma studied with in vivo iododeoxyuridine administration, nuclear Ki-67 staining, and flow cytometry.
Blood
80:2336,
1992[Abstract/Free Full Text]
196.
Miller TP,
Grogan TM,
Dahlberg S,
Spier CM,
Braziel RM,
Banks PM,
Foucar K,
Kjeldsberg CR,
Levy N,
Nathwani BN,
Schnitzer B,
Tubbs RR,
Gaynor ER,
Fisher RI:
Prognostic significance of the Ki-67-associated proliferation antigen in aggressive non-Hodgkin's lymphomas: A prospective Southwest Oncology Group trial.
Blood
83:1460,
1994[Abstract/Free Full Text]
197.
Shivdasani RA,
Hess JL,
Skarin AT,
Pinkus GS:
Intermediate lymphocytic lymphoma: Clinical and pathologic features of a recently characterized subtype of non-Hodgkin's lymphoma.
J Clin Oncol
11:802,
1993[Abstract]
198.
Tolksdorf G,
Stein H,
Lennert K:
Morphological and immunological definition of a malignant lymphoma derived from germinal-centre cells with cleaved nuclei (centrocytes).
Br J Cancer
41:168,
1980[Medline]
[Order article via Infotrieve]
199.
Swerdlow SH,
Habeshaw JA,
Murray LJ,
Dhaliwal HS,
Lister TA,
Stansfeld AG:
Centrocytic lymphoma: A distinct clinicopathologic and immunologic entity.
Am J Pathol
113:181,
1983[Abstract]
200.
Harris NL,
Nadler LM,
Bhan AK:
Immunohistologic characterization of two malignant lymphomas of germinal center type (centroblastic/centrocytic and centrocytic) with monoclonal antibodies.
Am J Pathol
117:262,
1984[Abstract]
201.
De Oliveira MSP,
Jaffe ES,
Catovsky D:
Leukaemic phase of mantle zone (intermediate) lymphoma: Its characterisation in 11 cases.
J Clin Pathol
42:962,
1989[Abstract/Free Full Text]
202.
O'Briain DS,
Kennedy MJ,
Daly PA,
O'Brien AAJ,
Tanner WA,
Roger P,
Lawlor E:
Multiple lymphomatous polyposis of the gastrointestinal tract.
Am J Surg Pathol
13:691,
1989[Medline]
[Order article via Infotrieve]
203.
Zucca E,
Stein H,
Coiffier B:
European Lymphoma Task Force (ELTF ): Report of the workshop on mantle cell lymphoma (MCL).
Ann Oncol
5:507,
1994[Free Full Text]
204.
Lardelli P,
Bookman MA,
Sundeen J,
Longo DL,
Jaffe ES:
Lymphocytic lymphoma of intermediate differentiation.
Am J Surg Pathol
14:752,
1990[Medline]
[Order article via Infotrieve]
205.
Molot RJ,
Meeker TC,
Wittwer CT,
Perkins SL,
Segal GH,
Masih AS,
Braylan RC,
Kjeldsberg CR:
Antigen expression and polymerase chain reaction amplification of mantle cell lymphomas.
Blood
83:1626,
1994[Abstract/Free Full Text]
206.
Fisher RI,
Dahlberg S,
Nathwani BN,
Banks PM,
Miller TP,
Grogan TM:
A clinical analysis of two indolent lymphoma entities: Mantle cell lymphoma and marginal zone lymphoma (Including the mucosa-associated lymphoid tissue and monocytoid B-cell subcategories): A Southwest Oncology Group study.
Blood
85:1075,
1995[Abstract/Free Full Text]
207.
Teodorovic I,
Pittaluga S,
Kluin-Nelemans JC,
Meerwaldt JH,
Hagenbeek A,
van Glabbeke M,
Somers R,
Bijnens L,
Noordijk EM,
De Wolf-Peeters C for the European Organization for the Research and Treatment of Cancer Lymphoma Cooperative Group:
Efficacy of four different regimens in 64 mantle-cell lymphoma cases: Clinicopathologic comparison with 498 other non-Hodgkin's lymphoma subtypes.
J Clin Oncol
13:2819,
1995[Abstract]
208.
Coiffier B,
Hiddemann W,
Stein H:
Mantle cell lymphoma: A therapeutic dilemma.
Ann Oncol
6:208,
1995[Free Full Text]
209.
Medeiros LJ,
Van Kriekin JH,
Jaffe ES,
Raffeld M:
Association of bcl-1 rearrangements with lymphocytic lymphoma of intermediate differentiation.
Blood
76:2086,
1990[Abstract/Free Full Text]
210.
Williams ME,
Westerman CD,
Swerdlow SH:
Genotypic characterization of centrocytic lymphoma: Frequent rearrangement of the chromosome 11 bcl-1 locus.
Blood
76:1387,
1990[Abstract/Free Full Text]
211.
Leroux D,
Le Marc Hadour F,
Gressin R,
Jacob MC,
Keddari E,
Monteil M,
Caillot P,
Jalbert P,
Sotto JJ:
Non-Hodgkin's lymphomas with t(11; 14)(q13; q32): A subset of mantle zone/intermediate lymphocytic lymphoma?
Br J Haematol
77:346,
1991[Medline]
[Order article via Infotrieve]
212.
Rimokh R,
Berger F,
Delsol G,
Charrin C,
Bertheas MF,
Ffrench M,
Garoscio M,
Felman P,
Coiffier B,
Bryon PA,
Rochet M,
Gentilhomme O,
Germain D,
Magaud JP:
Rearrangement and overexpression of the BCL-1/PRAD-1 gene in intermediate lymphocytic lymphomas and in t(11q13)-bearing leukemias.
Blood
81:3063,
1993[Abstract/Free Full Text]
213.
Rimokh R,
Berger F,
Delsol G,
Digonnet I,
Rouault JP,
Tigaud JD,
Gadoux M,
Coiffier B,
Bryon PA,
Magaud JP:
Detection of the chromosomal translocation t(11; 14) by polymerase chain reaction in mantle cell lymphomas.
Blood
83:1871,
1994[Abstract/Free Full Text]
214.
de Boer CJ,
Schuuring E,
Dreef E,
Peters G,
Bartek J,
Kluin PM,
van Krieken JHJM:
Cyclin D1 protein analysis in the diagnosis of mantle cell lymphoma.
Blood
86:2715,
1995[Abstract/Free Full Text]
215.
Segal GH,
Masih AS,
Fox AC,
Jorgensen T,
Scott M,
Braylan RC:
CD5-expressing B-cell non-Hodgkin's lymphomas with bcl-1 gene rearrangement have a relatively homogeneous immunophenotype and are associated with an overall poor prognosis.
Blood
85:1570,
1995[Abstract/Free Full Text]
216.
Bosch F,
Jares P,
Campo E,
Lopez-Guillermo A,
Piris MA,
Villamor N,
Tassies D,
Jaffe ES,
Montserrat E,
Rozman C,
Cardesa A:
PRAD-1/Cyclin D1 gene overexpression in chronic lymphoproliferative disorders: A highly specific marker of mantle cell lymphoma.
Blood
84:2726,
1994[Abstract/Free Full Text]
217.
Louie DC,
Offit K,
Jaslow R,
Parsa NZ,
Murty VVVS,
Schluger A,
Chaganti RSK:
p53 overexpression as a marker of poor prognosis in mantle cell lymphomas with t(11; 14)(q13; q32).
Blood
86:2892,
1995[Abstract/Free Full Text]
218.
Jaffe ES,
Raffeld M,
Medeiros LJ,
Stetler-Stevenson M:
An overview of the classification of non-Hodgkin's lymphomas: An integration of morphological and phenotypical concepts.
Cancer Res
52:5447s,
1992[Abstract/Free Full Text]
219.
Longo DL:
What's the deal with follicular lymphomas?
J Clin Oncol
11:202,
1993[Free Full Text]
220.
Hollema H,
Poppema S:
Immunophenotypes of malignant lymphoma centroblastic-centrocytic and malignant lymphoma centrocytic: An immunohistologic study indicating a derivation from different stages of B cell differentiation.
Hum Pathol
19:1053,
1988[Medline]
[Order article via Infotrieve]
221.
Lambrechts AC,
Hupkes PE,
Dorssers LCJ,
van't Veer MB:
Translocation (14:18)-positive cells are present in the circulation of the majority of patients with localized (stage I and II) follicular non-Hodgkin's lymphoma.
Blood
82:2510,
1993[Abstract/Free Full Text]
222.
Weiss LM,
Warnke RA,
Sklar J,
Cleary ML:
Molecular analysis of the t(14; 18) chromosome translocation in malignant lymphomas.
N Engl J Med
371:1185,
1987
223.
Rowley JD:
Chromosome studies in the non-Hodgkin's lymphomas: The role of the 14; 18 translocation.
J Clin Oncol
6:919,
1988[Abstract/Free Full Text]
224.
Tilly H,
Rossi A,
Stamatoullas A,
Lenormand B,
Bigorgne C,
Kunlin A,
Monconduit M,
Bastard C:
Prognostic value of chromosomal abnormalities in follicular lymphoma.
Blood
84:1043,
1994[Abstract/Free Full Text]
225.
Dyer MJS,
Zani VJ,
Lu WZ,
O'Byrne A,
Mould S,
Chapman R,
Heward JM,
Kayano H,
Jadayel D,
Matutes E,
Catovsky D,
Oscier DG:
BCL2 translocations in leukemias of mature B cells.
Blood
83:3682,
1994[Abstract/Free Full Text]
226.
Limpens J,
Stad R,
Vos C,
de Vlaam C,
De Jong D,
van Ommen GJB,
Schuuring E,
Kluin PM:
Lymphoma-associated translocation t(14; 18) in blood B cells of normal individuals.
Blood
85:2528,
1995[Abstract/Free Full Text]
227.
Limpens J,
De Jong D,
Van Krieken JHJM,
Price CGA,
Young BD,
van Ommen G-JB,
Kluin PhM:
BCL-2/JH rearrangements in benign lymphoid tissues with follicular hyperplasia.
Oncogene
6:2271,
1991[Medline]
[Order article via Infotrieve]
228.
Lambrects AC,
Hupkes PE,
Dorssers LCJ,
van't Veer MB:
Clinical significance of t(14:18)-positive cells in the circulation of patients with stage III or IV follicular non-Hodgkin's lymphoma during first remission.
J Clin Oncol
12:1541,
1994[Abstract/Free Full Text]
229.
Gribben JG,
Freedman AS,
Neuberg D,
Roy DC,
Blake KW,
Woo SD,
Grossbard ML,
Rabinowe SN,
Coral F,
Freeman GJ,
Ritz J,
Nadler LM:
Immunologic purging of marrow assessed by PCR before autologous bone marrow transplantation for B-cell lymphoma.
N Engl J Med
325:1525,
1991[Abstract]
230.
Gribben JG,
Neuberg D,
Freedman AS,
Gimmi CD,
Pesek KW,
Barber M,
Saporito L,
Woo SD,
Coral F,
Spector N,
Rabinowe SN,
Grossbard ML,
Ritz J,
Nadler LM:
Detection by polymerase chain reaction of residual cells with the bcl-2 translocation is associated with increased risk of relapse after autologous bone marrow transplantation for B-cell lymphoma.
Blood
81:3449,
1993[Abstract/Free Full Text]
231.
Johnson PWM,
Price CGA,
Smith T,
Cotter FE,
Meeabux J,
Rohatiner AZS,
Young BD,
Lister TA:
Detection of cells bearing the t(14; 18) translocation following myeloablative treatment and autologous bone marrow transplantation for follicular lymphoma.
J Clin Oncol
12:798,
1994[Abstract]
232.
Cleary ML,
Galili N,
Trela M,
Levy R,
Sklar J:
Single cell origin of bigenotypic and biphenotypic B cell proliferations in human follicular lymphomas.
J Exp Med
167:582,
1988[Abstract/Free Full Text]
233.
Whang-Peng J,
Knutsen T,
Jaffe ES,
Steinberg SM,
Raffeld M,
Zhao WP,
Duffey P,
Condron K,
Yano T,
Longo DL:
Sequential analysis of 43 patients with non-Hodgkin's lymphoma: Clinical correlations with cytogenetic, histologic immunophenotyping, and molecular studies.
Blood
85:203,
1995[Abstract/Free Full Text]
234.
Sander CA,
Yano T,
Clark HM,
Harris C,
Longo DL,
Jaffe ES,
Raffeld M:
p53 mutation is associated with progression in follicular lymphomas.
Blood
82:1994,
1993[Abstract/Free Full Text]
235.
Lo Coco F,
Gaidano G,
Louie DC,
Offit K,
Chaganti RSK,
Dalla-Favera R:
p53 mutations are associated with histologic transformation of follicular lymphoma.
Blood
82:2289,
1993[Abstract/Free Full Text]
236.
Ichikawa A,
Hotta T,
Takagi N,
Tsushita K,
Kinoshita T,
Nagai H,
Murakami Y,
Hayashi K,
Saito H:
Mutations of p53 gene and their relation to disease progression in B-cell lymphoma.
Blood
79:2701,
1992[Abstract/Free Full Text]
237.
Yano T,
Jaffe ES,
Longo DL,
Raffeld M:
MYC rearrangements in histologically progressed follicular lymphomas.
Blood
80:758,
1992[Abstract/Free Full Text]
238.
De Jong D,
Voetdijk BMH,
Beverstock GC,
van Ommen GJB,
Willemze R,
Kluin PM:
Activation of the c-myc oncogene in a precursor-B-cell blast crisis of follicular lymphoma, presenting as composite lymphoma.
N Engl J Med
318:1373,
1988[Medline]
[Order article via Infotrieve]
239.
Villuendas R,
Piris MA,
Algara P,
Sanchez-Beato M,
Sanchez-Verde L,
Martinez JC,
Orradre JL,
Garcia P,
Lopez C,
Martinez P:
The expression of p53 protein in non-Hodgkin's lymphomas is not always dependent on p53 gene mutations.
Blood
82:3151,
1993[Abstract/Free Full Text]
240.
Sheibani K,
Burke JS,
Swartz WG:
Monocytoid B-cell lymphoma: A novel B-cell neoplasm.
Am J Pathol
124:310,
1986[Abstract]
241.
Isaacson PG,
Spencer J:
Malignant lymphoma of mucosa-associated lymphoid tissue.
Histopathology
11:445,
1987[Medline]
[Order article via Infotrieve]
242.
Sheibani K,
Burke JS,
Swartz WG,
Nademanee A,
Winberg CD:
Monocytoid B-cell lymphoma: Clinicopathologic study of 21 cases of a unique type of low-grade lymphoma.
Cancer
62:1531,
1988[Medline]
[Order article via Infotrieve]
243.
Diss TC,
Peng H,
Wotherspoon AC,
Pan L,
Speight PM,
Isaacson PG:
Brief report: A single neoplastic clone in sequential biopsy specimens from a patient with primary gastric-mucosa-associated lymphoid-tissue lymphoma and Sjogren's syndrome.
N Engl J Med
329:172,
1993[Free Full Text]
244.
Pelstring RJ,
Essell JH,
Kurtin PJ,
Cohen AR,
Banks PM:
Diversity of organ site involvement among malignant lymphomas of mucosa-associated tissues.
Am J Clin Pathol
96:738,
1991[Medline]
[Order article via Infotrieve]
245.
Qin BY,
Greiner A,
Trunk MJF,
Schmausser B,
Ott MM,
Muller-Hermelink HK:
Somatic hypermutation in low-grade mucosa-associated lymphoid tissue-type B-cell lymphoma.
Blood
86:3528,
1995[Abstract/Free Full Text]
246.
Hussell T,
Isaacson P,
Crabtree J,
Spencer J:
The response of cells from low-grade B-cell gastric lymphomas of mucosa-associated lymphoid tissue to Helicobacter pylori.
Lancet
342:571,
1993[Medline]
[Order article via Infotrieve]
247.
Wotherspoon A,
Doglioni C,
Diss T,
Pan L,
Moschini A,
de Boni M,
Isaacson P:
Regression of primary low-grade B-cell gastric lymphoma of mucosa-associated lymphoid tissue type after eradication of Helicobacter pylori.
Lancet
342:575,
1993[Medline]
[Order article via Infotrieve]
248.
Wotherspoon AC,
Finn TM,
Isaacson PG:
Trisomy 3 in low-grade B-cell lymphomas of mucosa-associated lymphoid tissue.
Blood
85:2000,
1995[Abstract/Free Full Text]
249.
Jadayel D,
Matutes E,
Dyer MJS,
Brito-Babapulle V,
Khohkar MT,
Oscier D,
Catovsky D:
Splenic lymphomas with villous lymphocytes: Analysis of BCL-1 rearrangements and expression of the cyclin D1 gene.
Blood
83:3664,
1994[Abstract/Free Full Text]
250.
Zhu D,
Oscier DG,
Stevenson FK:
Splenic lymphoma with villous lymphocytes involves B cells with extensively mutated Ig heavy chain variable region genes.
Blood
85:1603,
1995[Abstract/Free Full Text]
251.
Matutes E,
Morilla R,
Owusu-Ankomah K,
Houlihan A,
Catovsky D:
The immunophenotype of splenic lymphoma with villous lymphocytes and its relevance to the differential diagnosis with other B-cell disorders.
Blood
83:1558,
1994[Abstract/Free Full Text]
252.
Isaacson PG,
Matutes E,
Burke M,
Catovsky D:
The histopathology of splenic lymphoma with villous lymphocytes.
Blood
84:3828,
1994[Abstract/Free Full Text]
253.
Foroni L,
Catovsky D,
Luzzatto L:
Immunoglobulin gene rearrangements in hairy cell leukemia and other chronic B cell lymphoproliferative disorders.
Leukemia
4:389,
1987
254.
Visser L,
Shaw A,
Slupsky J,
Vos H,
Poppema S:
Monoclonal antibodies reactive with hairy cell leukemia.
Blood
74:320,
1989[Abstract/Free Full Text]
255.
Mulligan SP,
Travada P,
Matutes E,
Dearden C,
Visser L,
Poppema S Catovsky D:
B-ly7, a monoclonal antibody reactive with hairy cell leukemia, also defines an activation antigen on normal CD8+ T cells.
Blood
76:959,
1990[Abstract/Free Full Text]
256.
Micklem KJ,
Dong Y,
Willis A,
Pulford KA,
Visser L,
Durkop H,
Poppema S,
Stein H,
Mason DY:
HML-1 antigen on mucosa-associated T cells, activated cells, and hairy leukemic cells is a new integrin containing the 7 subunit.
Am J Pathol
139:1297,
1991[Abstract]
257.
Juliusson G,
Heldal D,
Hippe E,
Hedenus M,
Malm C,
Wallman K,
Stolt CM,
Evenson SA,
Albertioni F,
Tjonnfjord G,
Lenkei R,
Liliemark J:
Subcutaneous injection of 2-chlorodeoxyadenosine for symptomatic hairy cell leukemia.
J Clin Oncol
13:989,
1995[Abstract]
258.
Ellison DJ,
Sharpe RW,
Robbins BA,
Spinosa JC,
Leopard JD,
Saven A,
Piro LD:
Immunomorphologic analysis of bone marrow biopsies after treatment with 2-chlorodeoxyadenosine for hairy cell leukemia.
Blood
84:4310,
1994[Abstract/Free Full Text]
259.
Wheaton S,
Tallman MS,
Hakimian D,
Peterson L:
Minimal residual disease may predict bone marrow relapse in patients with hairy cell leukemia treated with 2-chlorodeoxyadenosine.
Blood
87:1556,
1996[Abstract/Free Full Text]
260.
Totero D,
Tazzari PL,
Lauria F,
Raspadori D,
Celle PF,
Carborne A,
Gobbi M,
Foa R:
Phenotypic analysis of hairy cell leukemia: Variant cases express the interleukin-2 receptor chain, but not the chain (CD25).
Blood
82:528,
1993[Abstract/Free Full Text]
261.
Estey EH,
Kurzrock R,
Kantarjian HM,
O'Brien SM,
McCredie KB,
Beran M,
Koller C,
Keating MJ,
Hirsh-Ginsberg C,
Huh YO,
Stass S,
Freireich EJ:
Treatment of hairy cell leukemia with 2-chlorodeoxyadenosine (2-CdA).
Blood
79:882,
1992[Abstract/Free Full Text]
262.
Piro LD,
Carrera CJ,
Carson DA,
Beutler E:
Lasting remissions in hairy-cell leukemia induced by a single infusion of 2-chlorodeoxyadenosine.
N Engl J Med
322:1117,
1990[Abstract]
263.
Seymore JF,
Kurzrock R,
Freireich EJ,
Estey EH:
2-Chlorodeoxyadenosine induces durable remissions and prolonged suppression of CD4+ lymphocyte counts in patients with hairy cell leukemia.
Blood
83:2906,
1994[Abstract/Free Full Text]
264.
Juliusson G,
Lenkei R,
Liliemark J:
Flow cytometry of blood and bone marrow cells from patients with hairy cell leukemia: Phenotype of hairy cells and lymphocyte subsets after treatment with 2-chlorodeoxyadenosine.
Blood
83:3672,
1994[Abstract/Free Full Text]
265.
Kampmeier P,
Spielberger R,
Dickstein J,
Mick R,
Golomb H,
Vardiman JW:
Increased incidence of second neoplasms in patients treated with interferon 2b for hairy cell leukemia: A clinicopathologic assessment.
Blood
83:2931,
1994[Abstract/Free Full Text]
266.
Goto BT,
Kennel SJ,
Abe M,
Takishita M,
Kosaka M,
Soloman A,
Saito S:
A novel membrane antigen selectively expressed on terminally differentiated human B cells.
Blood
84:1922,
1994[Abstract/Free Full Text]
267.
Van Zaanen HCT,
Vet RJWM,
De Jong CM,
Von Dem Borne AEGKr,
Van Oers MHJ:
A simple and sensitive method for determining plasma cell isotype and monoclonality in bone marrow using flow cytometry.
Br J Haematol
91:55,
1995[Medline]
[Order article via Infotrieve]
268.
Witzig TE,
Kimlinger TK,
Ahmann GJ,
Greipp PR:
Detection of peripheral blood myeloma cells by three-color flow cytometry.
Curr Top Microbiol Immunol
194:3,
1995[Medline]
[Order article via Infotrieve]
269.
Hata H,
Xiao H,
Petrucci MT,
Woodliff J,
Chang R,
Epstein J:
Interleukin-6 gene expression in multiple myeloma: A characteristic of immature tumor cells.
Blood
81:3357,
1993[Abstract/Free Full Text]
270.
Harada H,
Kawano MM,
Huang N,
Harada Y,
Iwato K,
Tanabe O,
Tanaka H,
Sakai A,
Asaoku H,
Kuramoto A:
Phenotypic difference of normal plasma cells from mature myeloma cells.
Blood
81:2658,
1993[Abstract/Free Full Text]
271.
Kawano M,
Huang N,
Harada H,
Harada Y,
Sakai A,
Tanaka H,
Iwato K,
Kuramoto A:
Identification of immature and mature myeloma cells in the bone marrow of human myelomas.
Blood
82:564,
1993[Abstract/Free Full Text]
272.
Pellat-Deceunynck C,
Bataille R,
Robillard N,
Harousseau JL,
Rapp MJ,
Juge-Morineau N,
Wijdenes J,
Amiot M:
Expression of CD28 and CD40 in human myeloma cells: A comparitive study with normal plasma cells.
Blood
84:2597,
1994[Abstract/Free Full Text]
273. Pilarski LM, Belch AR. Circulating monoclonal B cells expressing P glycoprotein may be a reservoir of multidrug-resistant disase in multiple myeloma. Blood 83:724, 1994
274.
Bergsagel PL,
Smith AM,
Szczepek A,
Mant MJ,
Belch AR,
Pilarski LM:
In multiple myeloma, clonotypic B lymphocytes are detectable among CD19+ peripheral blood cells expressing CD38, CD56, and monotypic Ig light chain.
Blood
85:436,
1995[Abstract/Free Full Text]
275.
Klein B,
Zhang XG,
Lu ZY,
Bataille R:
Interleukin-6 in human multiple myeloma.
Blood
85:863,
1995[Free Full Text]
276.
Billadeau D,
Quam L,
Thomas W,
Kay N,
Greipp P,
Kyle R,
Oken MM,
Van Ness B:
Detection and quantitation of malignant cells in the peripheral blood of multiple myeloma patients.
Blood
80:1818,
1992[Abstract/Free Full Text]
277.
Billadeau D,
Blackstadt M,
Greipp P,
Kyle RA,
Oken MM,
Kay N,
Van Ness B:
Analysis of B-lymphoid malignancies using allele-specific polymerase chain reaction: A technique for sequential quantitation of residual disease.
Blood
78:3021,
1991[Abstract/Free Full Text]
278.
Tricot G,
Jagannath S,
Vesole D,
Nelson J,
Tindle S,
Miller L,
Cheson B,
Crowley J,
Barlogie B:
Peripheral blood stem cell transplants for multiple myeloma: Identification of favorable variables for rapid engraftment in 225 patients.
Blood
85:588,
1995[Abstract/Free Full Text]
279.
Vescio RA,
Hong CH,
Cao J,
Kim A,
Schiller GJ,
Lichtenstein AK,
Berenson RJ,
Berenson JR:
The hematopoietic stem cell antigen, CD34, is not expressed on the malignant cells in multiple myeloma.
Blood
84:3283,
1994[Abstract/Free Full Text]
280.
Gazitt Y,
Reading CC,
Hoffman R,
Wickrema A,
Vesole DH,
Jagannath S,
Condino J,
Lee B,
Barlogie B,
Tricot G:
Purified CD34+ Lin- Thy+ stem cells do not contain clonal myeloma cells.
Blood
86:381,
1995[Abstract/Free Full Text]
281.
Dimopoulos MA,
Goldstein J,
Fuller L,
Delasalle K,
Alexanian R:
Curability of solitary bone plasmacytoma.
J Clin Oncol
10:587,
1992[Abstract/Free Full Text]
282.
Alexanian R,
Dimopoulos M:
The treatment of multiple myeloma.
N Engl J Med
330:484,
1994[Free Full Text]
283.
Herrinton LJ,
Weiss NS:
Incidence of Waldenstrom's macroglobulinemia.
Blood
82:3148,
1993[Abstract/Free Full Text]
284.
Facon T,
Brouillard M,
Duhamel A,
Morel P,
Simon M,
Jouet JP,
Bauters F,
Fenaux P:
Prognostic factors in Waldenstrom's macroglobulinemia: A report of 167 cases.
J Clin Oncol
11:1553,
1993[Abstract/Free Full Text]
285.
Dimopoulos MA,
Alexanian R:
Waldenstrom's macroglobulinemia.
Blood
83:1452,
1994[Free Full Text]
286.
Foon KA,
Gale RP:
Is there a T-cell form of chronic lymphocytic leukemia: Fact or fiction?
Leukemia
6:876,
1992
287.
Matutes E,
Brito-Babapulle V,
Swansbury J,
Ellis J,
Morilla R,
Dearden C,
Sempere A,
Catovsky D:
Clinical and laboratory features of 78 cases of T-prolymphocytic leukemia.
Blood
78:3269,
1991[Abstract/Free Full Text]
288.
Dohner H,
Ho AD,
Thaler J,
Stryckmans P,
Sonneveld P,
de Witte T,
Lechner K,
Lauria F,
Bodewadt-Radzun Suciu S,
Solbu G,
Witt B,
Hunstein W,
Zittoun R:
Pentostatin in prolymphocytic leukemia: Phase II trial of the European Organization for Research and Treatment of Cancer Leukemia Cooperative Study Group.
J Natl Cancer Inst
85:658,
1993[Abstract/Free Full Text]
289.
Reynold CW,
Foon KA:
T gamma-lymphoproliferative disorders in man and experimental animals: A review of the clinical, cellular, and functional characteristics.
Blood
64:1146,
1984[Abstract/Free Full Text]
290.
Tefferi A,
Li CY,
Witzig TE,
Dhodapkar MV,
Okuno SH,
Phyliky RL:
Chronic natural killer cell lymphocytosis: A descriptive clinical study.
Blood
84:2721,
1994[Abstract/Free Full Text]
291.
Dhodapkar MV,
Li CY,
Lust JA,
Tefferi A,
Phyliky RL:
Clinical spectrum of clonal proliferations of T-large granular lymphocytes: A T-cell clonopathy of undetermined significance?
Blood
84:1620,
1994[Abstract/Free Full Text]
292.
Loughran TP:
Clonal diseases of large granular lymphocytes.
Blood
82:1,
1993[Abstract/Free Full Text]
293.
Scott CS,
Richards SJ:
Classification of large granular lymphocyte (LGL) and NK-associated (Nka) disorders.
Blood Rev
6:220,
1992[Medline]
[Order article via Infotrieve]
294.
Nichols GE,
Normansell DE,
Williams ME:
Lymphoproliferative disorder of granular lymphocytes: Nine cases including one with features of CD56 (NKH1)-positive aggressive natural killer cell lymphoma.
Mod Pathol
7:819,
1994[Medline]
[Order article via Infotrieve]
295.
Gentile TC,
Uner AH,
Hutchison RE,
Wright J,
Ben-Ezra J,
Russell EC,
and Loughran TP:
CD3+, CD56+ aggressive variant of large granular lymphocyte leukemia.
Blood
84:2315,
1994[Abstract/Free Full Text]
296.
Wong KF,
Chan JKC,
Matutes E,
McCarthy K,
Chan CH,
Ma SK:
Hepatosplenic T-cell lymphoma: A distinctive aggressive lymphoma type.
Am J Surg Pathol
19:718,
1995[Medline]
[Order article via Infotrieve]
297.
Sallah S,
Smith SV,
Lony LC,
Woddard P,
Schmitz JL,
Folds JD:
Gamma/delta T-cell hepatosplenic lymphoma: Review of the literature, diagnosis by flow cytometry and concomitant autoimmune hemolytic anemia.
Ann Hematol
74:139,
1997[Medline]
[Order article via Infotrieve]
298.
Theodorou I,
Delfau-Larue MH,
Bigorgne C,
Lahet C,
Cochet G,
Bagot M,
Wechsler J,
Farcet JP:
Cutaneous T-cell infiltrates: Analysis of T-cell receptor gene rearrangement by polymerase chain reaction and denaturing gradient gel electrophoresis.
Blood
86:305,
1995[Abstract/Free Full Text]
299.
Bottaro M,
Berti E,
Biondi A,
Migone N,
Crosti L:
Heteroduplex analysis of T-cell receptor gene rearrangements for diagnosis and monitoring of cutaneous T-cell lymphomas.
Blood
83:3271,
1994[Abstract/Free Full Text]
300.
Lynch JW,
Linoilla L,
Sausville EA,
Steinberg SM,
Ghosh BC,
Nguyen DT,
Schechter GP,
Fischmann AB,
Ihde DC,
Stocker JL,
Bastian A,
Turner R,
Cotelingam JD,
Gazdar AF,
Foss FM:
Prognostic implications of evaluation for lymph node involvement by T-cell antigen receptor gene rearrangement in mycosis fungoides.
Blood
79:3293,
1992[Abstract/Free Full Text]
301.
Wolfe JT,
Chooback L,
Finn DT,
Jaworsky Rook AH,
Lessin S:
Large-cell transformation following detection of minimal residual disease in cutaneous T-cell lymphoma: Molecular and in situ analysis of a single neoplastic T-cell clone expressing the identical T-cell receptor.
J Clin Oncol
13:1751,
1995[Abstract/Free Full Text]
302.
Joly P,
Charlotte F,
Leibowitch M,
Haioun C,
Wechsler J,
Dreyfus F,
Escande JP,
Revuz J,
Reyes F,
Varet B,
Bagot M:
Cutaneous lymphomas other than mycosis fungoides: Follow-up study of 52 patients.
J Clin Oncol
9:1994,
1991[Abstract/Free Full Text]
303.
Neri A,
Fracchiolla NS,
Roscetti E,
Garatti S,
Trecca D,
Boletini A,
Perletti L,
Baldini L,
Maiolo AT,
Berti E:
Molecular analysis of cutaneous B- and T-cell lymphomas.
Blood
86:3160,
1995[Abstract/Free Full Text]
304.
Ghosh SK,
Abrams JT,
Terunuma H,
Vonderheid EC,
DeFreitas E:
Human T-cell leukemia virus type I tax/rex DNA and RNA in cutaneous T-cell lymphoma.
Blood
84:2663,
1994[Abstract/Free Full Text]
305.
Zucker-Franklin D,
Hooper WC,
Evatt BL:
Human lymphotropic retroviruses associated with mycosis fungoides: Evidence that human T-cell lymphotropic virus type II (HTLV-II) as well as HTLV-I may play a role in the disease.
Blood
80:1537,
1992[Abstract/Free Full Text]
306.
Manns A,
Cleghorn FR,
Falk RT,
Hanchard B,
Jaffe ES,
Bartholomew C,
Hartge P,
Benichou J,
Blattner WA,
The HTLV Lymphoma Study Group:
Role of HTLV-I development of non-Hodgkin lymphoma in Jamaica and Trinidad and Tobago.
Lancet
342:1447,
1993[Medline]
[Order article via Infotrieve]
307.
Yamaguchi K:
Human T-lymphotropic virus type I in Japan.
Lancet
343:213,
1994[Medline]
[Order article via Infotrieve]
308.
Waldmann TA,
White JD,
Goldman CK,
Top L,
Grant A,
Bamford R,
Roessler E,
Horak ID,
Zaknoen Kasten-Sportes C,
England R,
Horak E,
Mishra B,
Dipre M,
Hale P,
Fleisher TA,
Junghans RP,
Jaffe ES,
Nelson DL:
The interleukin-2 receptor: A target for monoclonal antibody treatment of human T-cell lymphotrophic virus I-induced adult T-cell leukemia.
Blood
82:1701,
1993[Abstract/Free Full Text]
309.
Suzushima H,
Hattori T,
Asou N,
Wang JX,
Nishikawa K,
Okubo T,
Anderson P,
Takatsuki K:
Discordant gene and surface expression of the T-cell receptor/CD3 complex in adult T-cell leukemia cells.
Cancer Res
51:6084,
1991[Abstract/Free Full Text]
310.
Tatewaki M,
Yamaguchi K,
Matsuoka M,
Ishii T,
Miyasaka M,
Mori S,
Takatsuki K,
Watanabe T:
Constitutive overexpression of the L-selectin gene in fresh leukemic cells of adult T-cell leukemia that can be transactivated by human T-cell lymphotropic virus type 1 tax.
Blood
86:3109,
1995[Abstract/Free Full Text]
311.
Cesarman E,
Chadburn A,
Inghirami G,
Gaidano G,
Knowles DM:
Structural and functional analysis of oncogenes and tumor suppressor genes in adult T-cell leukemia/lymphoma shows frequent p53 mutations.
Blood
80:3205,
1992[Abstract/Free Full Text]
312.
Sakashita A,
Hattori T,
Miller CW,
Suzushima H,
Asou N,
Takatsuki K,
Koeffler HP:
Mutations of the p53 gene in adult T-cell leukemia.
Blood
79:477,
1992[Abstract/Free Full Text]
313.
Feller AC,
Griesser GH,
Mak TW,
Lennert K:
Lymphoepithelioid lymphoma (Lennert's lymphoma) is a monoclonal proliferation of helper/inducer T-cells.
Blood
68:663,
1986[Abstract/Free Full Text]
314.
Stonesifer KJ,
Benson NA,
Ryden SE,
Pawliger DF,
Braylan RC:
The malignant cells in a Lennert's lymphoma are T lymphocytes with a mature helper surface phenotype. A multiparameter flow cytometric analysis.
Blood
68:426,
1986[Abstract/Free Full Text]
315.
Lipford EH,
Margolick JB,
Longo DL,
Fauci AS,
Jaffe ES:
Angiocentric immunoproliferative lesions: A clinicopathologic spectrum of post-thymic T-cell proliferations.
Blood
72:1674,
1988[Abstract/Free Full Text]
316.
Medeiros LF,
Peiper SC,
Elwood L,
Yano T,
Raffeld M,
Jaffe ES:
Angiocentric immunoproliferative lesions: A molecular analysis of eight cases.
Hum Pathol
22:1150,
1991[Medline]
[Order article via Infotrieve]
317.
Tsai TF,
Su IJ,
Lu YC,
Cheng AL,
Yeh HP,
Hsieh HC,
Tien HF,
Chen JS,
Uen WC:
Cutaneous angiocentric T-cell lymphoma associated with Epstein-Barr virus.
J Am Acad Dermatol
29:31,
1992
318.
Kueck BD,
Hanson CA,
Weissman DE,
Bayliss K:
Primary lymph node presentation of angiocentric lymphoma associated with features of a hemophagocytic syndrome.
Am J Hematol
30:111,
1989
319.
Darbesio A,
Ferrero D:
Angiocentric lymphoma: A case report.
Haematologica
75:381,
1990[Medline]
[Order article via Infotrieve]
320.
Foss HD,
Anagnostopoulos I,
Herbst H,
Grebe M,
Ziemann K,
Hummel M,
Stein H:
Patterns of cytokine gene expression in peripheral T-cell lymphoma of angioimmunoblastic lymphadenopathy type.
Blood
85:2862,
1995[Abstract/Free Full Text]
321.
Hoyer JD,
Ross CW,
Li CY,
Witzig TE,
Gascoyne RD,
Dewald GW,
Hanson CA:
True T-cell chronic lymphocytic leukemia: A morphologic and immunophenotypic study of 25 cases.
Blood
86:1163,
1995[Abstract/Free Full Text]
322.
Schlegelberger B,
Himmler A,
Godde E,
Grote W,
Feller AC,
Lennert K:
Cytogenetic findings in peripheral T-cell lymphomas as a basis for distinguishing low-grade and high-grade lymphomas.
Blood
83:505,
1994[Abstract/Free Full Text]
323.
Siegert W,
Agthe A,
Griesser H,
Schwerdtfeger R,
Brittinger G,
Engelhard M,
Kuse R,
Tiemann M,
Lennert K,
Huhn D,
Kiel Lymphoma Study Group:
Treatment of angioimmunoblastic lymphadenopathy (AILD)-type T-cell lymphoma using prednisone with or without the COPBLAM/IMVP-16 regimen.
Ann Intern Med
117:364,
1992
324.
Gordon BG,
Warkentin PI,
Weisenburger DD,
Vose JM,
Sanger WG,
Strandjord SE,
Anderson JR,
Verdirame JD,
Bierman PJ,
Armitage JO,
Coccia PF:
Bone marrow transplantation for peripheral T-cell lymphoma in children and adolescents.
Blood
80:2938,
1992[Abstract/Free Full Text]
325.
Mercieca J,
Matutes E,
Dearden C,
MacLennan K,
Catovsky D:
The role of pentostatin in the treatment of T-cell malignancies: Analysis of response rate in 145 patients according to disease subtype.
J Clin Oncol
12:2588,
1994[Abstract/Free Full Text]
326.
Offit K,
Lo Coco F,
Louie DC,
Parsa NA,
Leung D,
Portlock C,
Ye BH,
Lista F,
Filippa DA,
Rosenbaum A,
Ladanyi M,
Jhanwar S,
Dalla-Favera R,
Chaganti RSK:
Rearrangement of the bcl-6 gene as a prognostic marker in diffuse large-cell lymphoma.
N Engl J Med
331:74,
1994[Abstract/Free Full Text]
327.
Hutchison RE,
Berard CW,
Shuster JJ,
Link MP,
Pick TE,
Murphy SB:
B-cell lineage confers a favorable outcome among children and adolescents with large-cell lymphoma: A pediatric oncology group study.
J Clin Oncol
13:2023,
1995[Abstract/Free Full Text]
328.
Lippman SM,
Miller TP,
Spier CM,
Slymen DJ,
Grogan TM:
The prognostic significance of the immunotype in diffuse large-cell lymphoma: A comparative study of the T-cell and B-cell phenotype.
Blood
72:436,
1988[Abstract/Free Full Text]
329.
Shipp MA:
Prognostic factor in aggressive non-Hodgkin's lymphoma: Who has "high risk" disease?
Blood
83:1165,
1994[Abstract/Free Full Text]
330.
Joensuu H,
Klemi PJ,
Jalkanen S:
Biologic progression in non-Hodgkin's lymphoma.
Cancer
65:2564,
1990[Medline]
[Order article via Infotrieve]
331.
Joensuu H,
Ristamaki R,
Soderstrom KO,
Jalkanen S:
Effect of treatment on the prognostic value of S-phase fraction in non-Hodgkin's lymphoma.
J Clin Oncol
12:2167,
1994[Abstract/Free Full Text]
332.
Bastard C,
Deweindt C,
Kerckaert JP,
Lenormand B,
Rossi A,
Pezzella F,
Fruchart C,
Duval C,
Monconduit M,
Tilly H:
LAZ3 rearrangements in non-Hodgkin's lymphoma: Correlation with histology, immunophenotype, karyotype, and clinical outcome in 217 patients.
Blood
83:2423,
1994[Abstract/Free Full Text]
333.
Greer JP,
Macon WR,
Lamar RE,
Wolff SN,
Stein RS,
Flexner JM,
Collins RD,
Cousar JB:
T-cell-rich B-cell lymphomas: Diagnosis and response to therapy of 44 patients.
J Clin Oncol
13:1742,
1995[Abstract/Free Full Text]
334.
Rodriguez J,
Pugh WC,
Cabanillas F:
T-cell-rich B-cell lymphoma.
Blood
82:1586,
1993[Abstract/Free Full Text]
335.
McBride JA,
Rodriguez J,
Luthra R,
Ordonez NG,
Cabanillas F,
Pugh WC:
T-cell-rich B large-cell lymphoma simulating lymphocyte-rich Hodgkin's disease.
Am J Surg Pathol
20:193,
1996[Medline]
[Order article via Infotrieve]
336.
Lazzarino M,
Orlandi E,
Paulli M,
Boveri E,
Morra E,
Brusamolino E,
Kindl S,
Rosso R,
Astori C,
Buonanno MC,
Magrini U,
Bernasconi C:
Primary mediastinal B-cell lymphoma with sclerosis: An aggressive tumor with distinctive clinical and pathologic features.
J Clin Oncol
11:2306,
1993[Abstract/Free Full Text]
337.
Cazals-Hatem D,
Lepage E,
Brice P,
Ferrant A,
d'Agay MF,
Baumelou E,
Briere J,
Blanc M,
Gaulard P,
Biron P,
Schlaifer D,
Diebold J,
Audouin J:
Primary mediastinal large B-cell lymphoma.
Am J Surg Pathol
20:877,
1996[Medline]
[Order article via Infotrieve]
338.
Kadin ME:
Ki-1/CD30+ (anaplastic) large cell lymphoma: Maturation of a clinicopathologic entity with prospects of effective therapy.
J Clin Oncol
12:884,
1994[Free Full Text]
339.
Falini B,
Pileri S,
Pizzolo G,
Durkop H,
Flenghi L,
Stirpe F,
Martelli MF,
Stein H:
CD30 (Ki-1) molecule: A new cytokine receptor of the tumor necrosis factor receptor superfamily as a tool for diagnosis and immunotherapy.
Blood
85:1,
1995[Free Full Text]
340.
Shulman LM,
Frisard B,
Antin JH,
Wheeler C,
Pinkus G,
Magauran N,
Mauch P,
Nobles E,
Mashal R,
Canellos G,
Tung N,
Kadin M:
Primary Ki-1 anaplastic large-cell lymphoma in adults: Clinical characteristics and therapeutic outcome.
J Clin Oncol
11:937,
1993[Abstract/Free Full Text]
341.
Sandlund JT,
Pui CH,
Santana VM,
Mahmoud H,
Roberts WM,
Morris S,
Raimondi S,
Ribeiro R,
Crist WM,
Lin JS,
Mao L,
Berard CW,
Hutchison RE:
Clinical features and treatment outcome for children with CD30+ large-cell non-Hodgkin's lymphoma.
J Clin Oncol
12:895,
1994[Abstract/Free Full Text]
342.
Kaudewitz P,
Stein H,
Dallenbach F,
Eckert F,
Bieber K,
Burg G,
Braun-Falco O:
Primary and secondary cutaneous Ki-1+ (CD30+) anaplastic large cell lymphomas: Morphologic immunohistologic and clinical characteristics.
Am J Pathol
135:359,
1989[Abstract]
343.
Paulli M,
Berti E,
Rosso R,
Boveri E,
Kindl S,
Klersy C,
Lazzarino M,
Borroni G,
Menestrina F,
Santucci M,
Gambini C,
Vassallo G,
Magrini U,
Sterry W,
Burg G,
Geerts ML,
Meijer CJLM,
Willamette R,
Feller AC,
Muller-Hermelink HK,
Kadin ME:
CD30/Ki-1-positive lymphoproliferative disorders of the skin  Clinicopathologic correlation and statistical analysis of 86 cases: A multicentric study from the European Organization for Research and Treatment of Cancer Cutaneous Lymphoma Project Group.
J Clin Oncol
13:1343,
1995[Abstract]
344.
Beljaards R,
Kaudewitz P,
Berti E,
Gianotti R,
Neumann C,
Rosso R,
Paulli M,
Meijer C,
Willemze R:
Primary cutaneous CD30-positive large cell lymphoma: Definition of a new type of cutaneous lymphoma with a favorable prognosis: A European multicenter study of 47 patients.
Cancer
71:2097,
1993[Medline]
[Order article via Infotrieve]
345.
Elmberger PG,
Lozano MD,
Weisenburger DD,
Sanger W,
Chan WC:
Transcripts of the npm-alk fusion gene in anaplastic large cell lymphoma, Hodgkin's disease, and reactive lymphoid lesions.
Blood
86:3517,
1995[Abstract/Free Full Text]
346.
Wellmann A,
Otsuki T,
Vogelbruch M,
Clark HM,
Jaffe ES,
Raffeld M:
Analysis of the t(2; 5)(p23; q35) translocation by reverse transcription-polymerase chain reaction in CD30+ anaplastic large-cell lymphomas, in other non-Hodgkin's lymphomas of T-cell phenotype, and in Hodgkin's disease.
Blood
86:2321,
1995[Abstract/Free Full Text]
347.
Downing JR,
Shurtleff SA,
Zielenska M,
Curcio-Brint AM,
Behm FG,
Head DR,
Sandlund JT,
Weisenburger DD,
Kossakowska AE,
Thorner P,
Lorenzana A,
Ladanyi M,
Morris SW:
Molecular detection of the (2; 5) translocation of non-Hodgkin's lymphoma by reverse transcriptase-polymerase chain reaction.
Blood
85:3416,
1995[Abstract/Free Full Text]
348.
Haluska FG,
Brufsky AM,
Canellos GP:
The cellular biology of the Reed-Sternberg cell.
Blood
84:1005,
1994[Free Full Text]
349.
Agnarsson B,
Kadin M:
The immunophenotype of Reed-Sternberg cells: A study of 50 cases of Hodgkin's disease using fixed frozen tissues.
Cancer
63:2083,
1989[Medline]
[Order article via Infotrieve]
350.
Falini B,
Stein R,
Pileri S,
Canino S,
Farabbi R,
Martelli M,
Grignani F,
Fagoli M,
Minelli O,
Ciani C,
Flenghi L:
Expression of lymphoid-associated antigens on Hodgkin's and Reed-Sternberg cells in Hodgkin's disease. An immunocytochemical study on lymph node cytospins using monoclonal antibodies.
Histopathology
11:1229,
1987[Medline]
[Order article via Infotrieve]
351.
Dallenbach F,
Stein H:
Expression of T-cell receptor beta chain in Reed-Sternberg cells.
Lancet
2:828,
1989[Medline]
[Order article via Infotrieve]
352.
Casey T,
Olson S,
Cousar J,
Collins R:
Immunophenotypes of Reed-Sternberg cells: A study of 19 cases of Hodgkin's disease in plastic embedded sections.
Blood
74:2624,
1989[Abstract/Free Full Text]
353.
Brinker M,
Poppema S,
Buys C,
Timens W,
Osinga J,
Visser L:
Clonal immunoglobulin gene rearrangements in tissues involved by Hodgkin's disease.
Blood
70:186,
1987[Abstract/Free Full Text]
354.
Weiss L,
Strickler J,
Hu E,
Warnke R,
Sklar J:
Immunoglobulin gene rearrangements in Hodgkin's disease.
Hum Pathol
17:1009,
1986[Medline]
[Order article via Infotrieve]
355.
Herbst H,
Tippelmann G,
Anagnostopoulos I,
Gertes J,
Schwarting R,
Boehm T,
Pileri S,
Jones D,
Stein H:
Immunoglobulin and T-cell receptor gene rearrangements in Hodgkin's disease and Ki-1 positive anaplastic large cell lymphoma: Dissociation between genotype and phenotype.
Leuk Res
13:103,
1989[Medline]
[Order article via Infotrieve]
356.
Knowles DM II,
Neri A,
Pelicci PG,
Burke JS,
Wu A,
Winberg CD,
Sheibani K,
Dalla-Favera R:
Immunoglobulin and T-cell receptor beta-chain gene rearrangement analysis of Hodgkin's disease: Implications for lineage determination and differential diagnosis.
Proc Natl Acad Sci USA
83:7942,
1986[Abstract/Free Full Text]
357.
Hummel M,
Ziemann K,
Lammert H,
Pileri S,
Sabattini E,
Stein H:
Hodgkin's disease with monoclonal and polyclonal populations of Reed-Sternberg cells.
N Engl J Med
333:901,
1995[Abstract/Free Full Text]
358.
Delabie J,
Tierens A,
Wu G,
Weisenburger DD,
Chan WC:
Lymphocyte predominance in Hodgkin's disease: Lineage and clonality determination using a single-cell assay.
Blood
84:3291,
1994[Abstract/Free Full Text]
359.
Küppers R,
Zhao M,
Hansmann M-L,
Rajewsky K:
Tracing B cell development in human germinal centres by molecular analysis of single cells picked from histological sections.
EMBO J
12:4955,
1993[Medline]
[Order article via Infotrieve]
360.
Teerenhovi L,
Lindholm C,
Pakkala A,
Franssila K,
Stein H,
Knuutila S:
Unique display of a pathologic karyotype in Hodgkin's disease by Reed-Sternberg cells.
Cancer Genet Cytogenet
34:305,
1988[Medline]
[Order article via Infotrieve]
361.
Cabanillas F,
Pathak S,
Trujillo J,
Grant G,
Cork A,
Hagemeister F,
Velasquez W,
McLaughlin P,
Redman J,
Katz R,
Butler J,
Freireich E:
Cytogenetic features of Hodgkin's disease suggest a possible origin from a lymphocyte.
Blood
71:1615,
1988[Abstract/Free Full Text]
362.
Schouten H,
Sanger W,
Duggan M,
Weisenberger D,
MacLennan K,
Armitage J:
Chromosomal abnormalities in Hodgkin's disease.
Blood
73:2149,
1989[Abstract/Free Full Text]
363.
Tilly H,
Bastard C,
Delastre T,
Duval C,
Bizet M,
Lenormand B,
Daunce J-P,
Monconduit M,
Piguet H:
Cytogenetic studies in untreated Hodgkin's disease.
Blood
77:1298,
1991[Abstract/Free Full Text]
364.
Cabanillas F:
A review and interpretation of cytogenetic abnormalities identified in Hodgkin's disease.
Hematol Oncol
6:271,
1988[Medline]
[Order article via Infotrieve]
365.
Poppema S,
Kaleta J,
Hepperle B:
Chromosomal abnormalities in patients with Hodgkin's disease: Evidence for frequent involvement of the 14q chromosomal region but infrequent bcl-2 gene rearrangement in Reed-Sternberg cells.
J Natl Cancer Inst
84:1789,
1992[Abstract/Free Full Text]
366.
Kadin M,
Muramoto L,
Said J:
Expression of T-cell antigens by Reed-Sternberg cells in Hodgkin's disease.
Am J Pathol
130:345,
1988[Abstract]
367.
Timens W,
Visser L,
Poppema S:
Nodular subtype perdominance type of Hodgkin's disease is a germinal center lymphoma.
Lab Invest
54:457,
1986[Medline]
[Order article via Infotrieve]
368.
Pinkus G,
Said J:
Hodgkin's disease, lymphocyte predomance type, nodular-further evidence for a B cell derivation.
Am J Pathol
133:211,
1988[Abstract]
369.
Stein H,
Hansmann M,
Lennert K,
Brandtzaeg P,
Gatter K,
Mason D:
Reed-Sternberg and Hodgkin cells in lymphocyte-predominant Hodgkin's disease of nodular subtype contain J-chain.
Am J Clin Pathol
96:292,
1986
370.
Hsu S,
Yang K,
Jaffe E:
Phenotypic expression of Hodgkin's and Reed-Sternberg cells in Hodgkin's disease.
Am J Pathol
118:209,
1985[Abstract]
371.
Delabie J,
Ceuppens JL,
Vandenberghe P,
de Boer M,
Coorevits L,
De Wolf-Peeters C:
The B7/BB1 antigen is expressed by Reed-Sternberg cells of Hodgkin's disease and contributes to the stimulating capacity of Hodgkin's disease-derived cell lines.
Blood
82:2845,
1993[Abstract/Free Full Text]
372.
Gruss H-J,
Hirschstein D,
Wright B,
Ulrich D,
Caligiuri MA,
Barcos M,
Strockbine L,
Armitage RJ,
Dower SK:
Expression and function of CD40 on Hodgkin and Reed-Sternberg cells and the possible relevance for Hodgkin's disease.
Blood
84:2305,
1994[Abstract/Free Full Text]
373.
Borowitz MJ,
Croker BP,
Metzgar RS:
Immunohistochemical analysis of the distribution of lymphocyte subpopulations in Hodgkin's disease.
Cancer Treat Rep
66:667,
1982[Medline]
[Order article via Infotrieve]
374.
Kawada H,
Watanabe S,
Yoshida M,
Fukuda R,
Kobayashi N,
Masumoto A,
Ogawa Y,
Ohbayashi Y,
Yonekura S,
Ichikawa Y:
Flow cytometric analysis of T-cell-rich B-cell lymphoma.
Acta Haematol
92:164,
1994[Medline]
[Order article via Infotrieve]
375.
Cline MJ:
Histiocytes and histiocytosis.
Blood
84:2840,
1994[Abstract/Free Full Text]
376. Chu T, Jaffe R: The normal Langerhans cell and the LCH cell. Br J Cancer 70:S4, 1994
377.
McLelland J,
Pritchard J,
Chu AC:
Histiocytosis-X: Current controversies.
Hematol Oncol Clin North Am
1:147,
1987[Medline]
[Order article via Infotrieve]
378.
Osband ME:
Cancer in children: Histiocytosis X.
Hematol Oncol Clin North Am
1:737,
1987[Medline]
[Order article via Infotrieve]
379.
Willman CL,
Busque L,
Griffith BB,
Favara BE,
McClain KL,
Duncan MH,
Gilliland DG:
Langerhans'-cell histiocytosis (Histiocytosis X) A clonal proliferative disease.
N Engl J Med
331:154,
1994[Abstract/Free Full Text]
380. Willman CL: Detection of clonal histiocytes in Langerhans cell histiocytosis: Biology and clinical significance: Br J Cancer 70:S29, 1994
381.
Writing Group of the Histiocyte Society:
Histiocytosis syndromes in children.
Lancet
1:208,
1987[Medline]
[Order article via Infotrieve]
382.
Gonzalez CL,
Jaffe ES:
The histiocytoses: Clinical presentation and differential diagnosis.
Oncology
4:47,
1990[Medline]
[Order article via Infotrieve]
383.
Jaffe ES,
Costa J,
Fauci AS,
Cossman J,
Tsokos M:
Malignant lymphoma and erythrophagocytosis simulating malignant histiocytosis.
Am J Med
75:741,
1983[Medline]
[Order article via Infotrieve]
384.
Falini B,
Pileri S,
De Solas I,
Martelli MF,
Mason DY,
Delsol G,
Gatter KC,
Fagioli M:
Peripheral T-cell lymphoma associated with hemophagocytic syndrome.
Blood
75:434,
1990[Abstract/Free Full Text]
385. Favara BE, Jaffe R, Chu B: The histiopathology of Langerhans cell histiocytosis. Br J Cancer 70:S17, 1994
386.
Goasguen JE,
Bennett JM:
Classification and morphologic features of the myelodysplastic syndromes.
Oncology
19:4,
1992
387.
Verhoef GE,
Boogaerts MA:
Cytogenetics and its prognostic value in myelodysplastic syndromes.
Acta Haematol
95:95,
1996[Medline]
[Order article via Infotrieve]
388.
San Miguel JF,
Hernandez JM,
Gonzalez-Sarmiento R,
Gonzalez M,
Sanchez I,
Orfao A,
Canizo MC,
Borrasca AL:
Acute leukemia after a primary myelodysplastic syndrome: Immunophenotypic, genotypic, and clinical characteristics.
Blood
78:768,
1991[Abstract/Free Full Text]
389.
Masuya M,
Kita K,
Shimizu N,
Ohishi K,
Katayama Sekine T,
Otsuji A,
Miwa H,
Shirakawa S:
Biologic characteristics of acute leukemia after myelodysplastic syndrome.
Blood
81:3388,
1993[Abstract/Free Full Text]
390.
Young NS,
Barrett AJ:
The treatment of severe acquired aplastic anemia.
Blood
85:3367,
1995[Free Full Text]
391.
Maciejewski J,
Selleri C,
Young MS:
Fas antigen expression on CD34+ human marrow cells is induced by interferon- and tumor necrosis factor- and potentiates hematopoietic suppression in vitro.
Blood
85:3183,
1995[Abstract/Free Full Text]
392.
Nistico A,
Young NS:
-Interferon gene expression in the bone marrow of patients with acquired aplastic anemia.
Ann Intern Med
120:463,
1994[Abstract/Free Full Text]
393.
Maciejewski JP,
Hibbs JR,
Anderson S,
Katevas P,
Young NS:
Bone marrow and peripheral blood lymphocyte phenotype in patients with bone marrow failure.
Exp Hematol
22:1102,
1994[Medline]
[Order article via Infotrieve]
394.
Hasle H,
Heim S,
Schroeder H,
Schmiegelow K,
Ostergaard E,
Kerndrup G:
Transient pancytopenia preceding acute lymphoblastic leukemia (pre-ALL).
Leukemia
9:605,
1995[Medline]
[Order article via Infotrieve]
395.
Matloub YH,
Brunning RD,
Arthur DC,
Ramsay NKC:
Severe aplastic anemia preceding acute lymphoblastic leukemia.
Cancer
71:264,
1993[Medline]
[Order article via Infotrieve]
396.
Liang R,
Chan TK,
Todd D:
Childhood acute lymphoblastic leukaemia and aplastic anaemia.
Leuk Lymphoma
13:411,
1994[Medline]
[Order article via Infotrieve]
397.
Armata J,
Grzeskowiak-Melanowska J,
Balwierz W,
Najbar-Pabian A,
Pawlik-Niesytto E:
Prognosis in acute lymphoblastic leukemia (ALL) in children preceded by an aplastic phase.
Leuk Lymphoma
13:517,
1994[Medline]
[Order article via Infotrieve]
398.
Reid MM,
Summerfield GP:
Distinction between aleukaemic prodrome of childhood acute lymphoblastic leukaemia and aplastic anaemia.
J Clin Pathol
8:697,
1992
399.
Kwong YL,
Lee CP,
Chan TK,
Chan LC:
Flow cytometric measurement of glycosylphosphatidyl-inostol-linked surface proteins on blood cells of patients with paroxysmal nocturnal hemoglobinuria.
Am J Clin Pathol
102:30,
1994[Medline]
[Order article via Infotrieve]
400.
Tooze JA,
Saso R,
Marsh JCW,
Papadopoulos A,
Pulford K,
Gordon-Smith EC:
The novel monoclonal antibody By114 helps detect the early emergence of a paroxysmal nocturnal hemoglobinuria clone in aplastc anemia.
Exp Hematol
23:1484,
1995[Medline]
[Order article via Infotrieve]
401.
Campana D,
Pui C-H:
Detection of minimal residual disease in acute leukemia: Methodologic advances and clinical significance.
Blood
85:1416,
1995[Free Full Text]
402. Campana D, Coustan-Smith E: The use of flow cytometry to detect minimal residual disease in acute leukemia. Eur J Histochem 40:39, 1996 (suppl 1)
403.
Sievers EL,
Loken MR:
Detection of minimal residual disease in acute myelogenous leukemia.
J Pediatr Hematol Oncol
17:123,
1995[Medline]
[Order article via Infotrieve]
404.
Stelzer GT:
Flow cytometric analysis of hematological malignancy: Multiparameter detection of residual tumor cells.
Clin Immunol
16:137,
1996
405.
Davis BH,
Szczarkowski W:
Detection of mantle cell lymphoma and low grade lymphoproliferative disorders.
Clin Immunol
16:143,
1996
406.
Van Dongen JJM,
Breit TH,
Adriaansen HJ,
Beishizen A,
Hooijkaas H:
Detection of minimal residual disease in acute leukemia by immunological marker analysis and polymerase chain reaction.
Leukemia
6:47,
1992
407.
Campana D,
Coustan-Smith E,
Behm FG:
The definition of remission in acute leukemia with immunologic techniques.
Bone Marrow Transplant
8:429,
1991[Medline]
[Order article via Infotrieve]
408.
Babusikova O,
Glasova M,
Kusenda J,
Konikova E,
Mesarosova A:
Flow cytometric determination of leukemia-associated marker combinations for the study of minimal residual disease.
Neoplasma
41:305,
1994[Medline]
[Order article via Infotrieve]
409.
Campana D:
Applications of cytometry to study acute leukemia: In vitro determination of drug sensitivity and detection of minimal residual disease.
Cytometry
18:68,
1994[Medline]
[Order article via Infotrieve]
410. Behm FG, Smith FO, Raimondi SC, Head D, Downing J, Bernstein I: Blasts of childhood acute lymphoblastic leukemia with translocations and inversions of chromosome 11q express a unique surface protein identified by MoAb 7.1. Mod Pathol 7:102a, 1994 (abstr)
411.
Slaper-Cortenbach ICM,
Admiraal LG,
Kerr JM,
Van Leeuwn EF,
Von dem Borne AEGK,
Tetteroo PAT:
Flow-cytometric detection of terminal deoxynucleotidyl transferase and other intracellular antigens in combination with membrane antigens in acute lymphoblastic leukemias.
Blood
72:1639,
1988[Abstract/Free Full Text]
412.
Drach J,
Gattringer C,
Huber H:
Combined flow cytometric assessment of cell surface antigens and nuclear TdT for the detection of minimal residual disease in acute leukemia.
Br J Haematol
77:37,
1991[Medline]
[Order article via Infotrieve]
413.
Macedo A,
Orfao A,
Ciudad J,
Gonzalez M,
Vidriales B,
Lopez-Berges MC,
Martinez A,
Landolfi C,
Canizo C,
San Miguel JF:
Phenotypic analysis of CD34 subpopulations in normal human bone marrow and its application for the detection of minimal residual disease.
Leukemia
9:1896,
1995[Medline]
[Order article via Infotrieve]
414.
Campana D,
Thompson JS,
Amlot P,
Brown S,
Janossy G:
The cytoplasmic expression of CD3 antigens in normal and malignant cells of the T lymphoid lineage.
J Immunol
138:648,
1987[Abstract]
415.
Janossy G,
Coustan-Smith E,
Campana D:
The reliability of cytoplasmic CD3 and CD22 antigen expression in the immunodiagnosis of acute leukemia A study of 500 cases.
Leukemia
3:170,
1988
416. Orfao A, Ciudad J, Lopez-Berges MC, Lopez A, Vidriales B, Caballero MD, Valverde B, Gonzalez M, San Miguel JF: Acute lymphoblastic leukemia (ALL): Detection of minimal residual disease (MRD) at flow cytometry. Leuk Lymphoma 13:87, 1994 (suppl 1)
417.
Adriaansen HJ,
Van Dongen JJ,
Kappers-Klunne MC,
Hahlen K,
Van't Veer MB,
Wijdenes de Bresser JH,
Holdrinet AC,
Harthoorn-Lasthizen EJ,
Abels J,
Hooijkaas H:
Terminal deoxynucleotidyl transferase positive subpopulations occur in the majority of ANLL: Implications for the detection of minimal disease.
Leukemia
4:404,
1990[Medline]
[Order article via Infotrieve]
418.
Coustan-Smith E,
Behm FG,
Hurwitz CA,
Rivera GK,
Campana D:
N-CAM (CD56) expression by CD34+ malignant myeloblasts has implications for minimal residual disease detection in acute myeloid leukemia.
Leukemia
7:853,
1993[Medline]
[Order article via Infotrieve]
419.
Lavabre-Bertrand T,
Poncelet P,
Janossy G:
Antigen density evaluation is a useful parameter in leukemia monitoring.
Leuk Lymphoma
13:118,
1994
420.
Syrjala M,
Anttila VJ,
Ruutu T,
Jansson SE:
Flow cytometric detection of residual disease in acute leukemia by assaying blasts co-expressing myeloid and lymphatic antigens.
Leukemia
8:1564,
1994[Medline]
[Order article via Infotrieve]
421.
Robertson LE,
Huh YO,
Butler JJ,
Pugh WC,
Hirsch-Ginsberg C,
Stass S,
Kantarjian H,
Keating MJ:
Response assessment in chronic lymphocytic leukemia after fludarabine plus prednisone: Clinical, pathologic, immunophenotypic, and molecular analysis.
Blood
80:29,
1992
422.
Adriaansen HJ,
Jacobs BC,
Kappers-Klunne MC,
Hahlen K,
Hooijkaas H,
Van Dongen JJM:
Detection of residual disease in AML patients by use of double immunologic marker analysis for terminal deoxynucleotidyl transferase and myeloid markers.
Leukemia
7:472,
1993[Medline]
[Order article via Infotrieve]
423. Carlo-Stella C, Mangoni L, Dotti GP, Rizzoli V: Techniques for detection of minimal residual disease. Leuk Lymphoma 18:75, 1995 (suppl 1)
424.
Roberts WM,
Estrov Z,
Ouspenskaia MS,
Johnston DA,
Mcclain KL,
Zipf TF:
Measurement of residual leukemia during remission in childhood acute lymphoblastic leukemia.
N Engl J Med
336:317,
1997[Abstract/Free Full Text]
425.
Gribben JG:
Attainment of molecular remission: A worthwhile goal?
J Clin Oncol
12:1532,
1994[Free Full Text]
426.
Nucifora G,
Larson RA,
Rowley JD:
Persistence of the 8; 21 translocation in patiens with acute myeloid leukemia type M2 in long-term remission.
Blood
82:712,
1993[Abstract/Free Full Text]
427.
Lee M-S,
Kantarjian H,
Talpaz M,
Freireich EJ,
Deisseroth A,
Trujillo JM,
Stass SA:
Detection of minimal residual disease by polymerase chain reaction in Philadelphia chromosome-positive chronic myelogenous leukemia following interferon therapy.
Blood
79:1920,
1992[Abstract/Free Full Text]
428.
Pichert G,
Alyea EP,
Soiffer RJ,
Roy DC,
Ritz J:
Persistence of myeloid progenitor cells expressing BCR-ABL mRNA after allogeneic bone marrow transplantation for chronic myelogenous leukemia.
Blood
84:2109,
1994[Abstract/Free Full Text]
429.
Miyamura K,
Tahara T,
Tanimoto M,
Morishita Y,
Kawashima K,
MorishimaY Saito H,
Tsuzuki S,
Takeyama K,
Kodera Y,
Matsuyama K,
Hirabayashi N,
Yamada H,
Naito K,
Imai K,
Sakamaki H,
Asai O,
Mizutani S:
Long persistent bcr-abl positive transcript detected by polymerase chain reaction after marrow transplant for chronic myelogenous leukemia without clinical relapse: A study of 64 patients.
Blood
81:1089,
1993[Abstract/Free Full Text]
430.
Radich JP,
Gehly G,
Gooley T,
Bryant E,
Clift RA,
Collins S,
Edmands S,
Kirk J,
Lee A,
Kessler P,
Schoch G,
Buckner CD,
Sullivan KM,
Appelbaum FR,
Thomas ED:
Polymerase chain reaction detection of the BCR-ABL fusion transcript after allogeneic marrow transplantation for chronic myeloid leukemia: Results and implications in 346 patients.
Blood
85:2632,
1995[Abstract/Free Full Text]
431.
Biernaux C,
Loos M,
Sels A,
Huez G,
Stryckmans P:
Detection of major bcr-abl gene expression at a very low level in blood cells of some healthy individuals.
Blood
86:3118,
1995[Abstract/Free Full Text]
432.
Beck WT,
Grogan TM,
Willman CL,
Cordon-Cardo C,
Parham DM,
Kuttesch JF,
Andreeff M,
Bates SE,
Berard CW,
Boyett JM,
Brophy NA,
Broxterman HJ,
Chan HSL,
Dalton WS,
Dietel M,
Fojo AT,
Gascoyne RD,
Head D,
Houghton PJ,
Srivastava DK,
Lehnert M,
Leith CP,
Paietta E,
Pavelic ZP,
Rimsza L,
Roninson IB,
Sikic BI,
Twentyman PR,
Warnke R,
Weinstein R:
Methods to detect P-glycoprotein-associated multidrug resistance in patients' tumors: Consensus recommendations.
Cancer Res
56:3010,
1996[Abstract/Free Full Text]
433.
Leith CP,
Kopecky KJ,
Godwin J,
McConnell T,
Slovak ML,
Chen I-M,
Head DR,
Appelbaum FR,
Willman CL:
Acute myeloid leukemia in the elderly: Assessment of multidrug resistance (MDR1) and cytogenetics distinguishes biologic subgroups with remarkably distinct responses to standard chemotherapy. A Southwest Oncology Group Study.
Blood
89:3323,
1997[Abstract/Free Full Text]
434.
te Boekhorst PA,
de Leeuw K,
Schoester M:
Predominance of functional multidrug resistence (MDR-1) phenotype in CD34+ acute myeloid leukemia cells.
Blood
82:3157,
1993[Abstract/Free Full Text]
435.
Leith CP,
Chen IM,
Kopecky KJ,
Appelbaum FR,
Head DR,
Goodwin JE,
Weick JK,
Willman CL:
Correlation of multidrug resistance (MDR1) protein expression with functional dye/drug efflux in acute myeloid leukemia by multiparameter flow cytometry: Identification of discordant MDR-/efflux+ and MDR1+/efflux-cases.
Blood
86:2329,
1995[Abstract/Free Full Text]
436.
Van Acker KL,
Van Hove LM,
Boogaerts MA:
Evaluation of flow cytometry for multidrug resistance detection in low resistance K562 cells using daunorubicin and monoclonal antibodies.
Cytometry
14:736,
1993[Medline]
[Order article via Infotrieve]
437.
Lacombe F,
Belloc F,
Dumain P,
Puntous M,
Makhoul PC,
Saux MC,
Bernard P,
Boisseau MR,
Reiffers J:
Detection of cytarabine resistance in patients with acute myelogenous leukemia using flow cytometry.
Blood
84:716,
1994[Abstract/Free Full Text]
438.
Grant CR,
Valdimarsson G,
Hipfner DR,
Almquist KC,
Cole SPC,
Deeley RG:
Overexpression of multidrug resistance-associated protein (MRP) increases resistance to natural product drugs.
Cancer Res
54:357,
1994[Abstract/Free Full Text]
439.
Kruh GD,
Chan A,
Myers K,
Gaughan K,
Miki T,
Aaronson SA:
Expression complementary DNA library transfer establishes mrp as a multidrug resistance gene.
Cancer Res
54:1649,
1994[Abstract/Free Full Text]
440.
Feller N,
Juiper CM,
Lankelma J,
Ruhdal JK,
Scheper RJ,
Pinedo HM,
Broxterman HJ:
Functional detection of MDR1/P170 and MRP/P190-mediated multidrug resistance in tumor cells by flow cytometry.
Br J Cancer
72:543,
1995[Medline]
[Order article via Infotrieve]
441.
Scheffer GL,
Wijngaard PLJ,
Flens MJ,
Izquierdo MA,
Slovak ML,
Pinedo HM,
Meijer CJLM,
Clever HC,
Scheper RJ:
The drug resistance-related protein LRP is the human major vault protein.
Nat Med
1:578,
1995[Medline]
[Order article via Infotrieve]
442.
List AF,
Spier SC,
Grogan TM,
Johnson C,
Roe DJ,
Gree JP,
Wolff SN,
Broxterman HJ,
Scheffer GL,
Scheper RJ,
Dalton WS:
Overexpression of the major vault transporter protein lung-resistance protein predicts treatment outcome in acute myeloid leukemia.
Blood
87:2464,
1996[Abstract/Free Full Text]
443.
Fisher DE:
Apoptosis in cancer therapy: Crossing the threshold.
Cell
78:539,
1994[Medline]
[Order article via Infotrieve]
444.
Symonds H,
Krall L,
Remington L,
Saenz-Robles M,
Lowe S,
Jacks T,
Van Dyke T:
p53-dependent apoptosis suppresses tumor growth and progression in vivo.
Cell
78:703,
1994[Medline]
[Order article via Infotrieve]
445.
Imamura J,
Miyoshi I,
Koeffler HP:
p53 in hematologic malignancies.
Blood
84:2412,
1994[Free Full Text]
446.
Wattel E,
Preudhomme C,
Hecquet B,
Vanrumbeke M,
Quesnel B,
Dervite I,
Morel P,
Fenaux P:
p53 mutations are associated with resistance to chemotherapy and short survival in hematologic malignancies.
Blood
84:3148,
1994[Abstract/Free Full Text]
447.
Campos L,
Rouault JP,
Sabido O,
Oriol P,
Roubi N,
Vasselon C,
Archimbaud E,
Magaud JP,
Guyotat D:
High expression of bcl-2 protein in acute myeloid leukemia cells is associated with poor response to chemotherapy.
Blood
81:3091,
1993[Abstract/Free Full Text]
448.
Prokocimer M,
Rotter V:
Structure and function of p53 in normal cells and their aberrations in cancer cells: Projection on the hematologic cell lineages.
Blood
84:2391,
1994[Free Full Text]
449.
McDonnell TJ:
The molecular regulation of apoptosis by oncogenes and tumor suppressor genes.
Adv Leuk Lymphoma
4:6,
1994
450.
Miyashita T,
Reed JC:
Bcl-2 oncoprotein blocks chemotherapy-induced apoptosis in a human leukemia cell line.
Blood
81:151,
1993[Abstract/Free Full Text]
451.
DiGiuseppe JA,
LeBeau P,
Augenbraun J,
Borowitz MJ:
Multiparameter flow-cytometric analysis of bcl-2 and Fas expression in normal and neoplastic hematopoiesis.
Am J Clin Pathol
106:345,
1996[Medline]
[Order article via Infotrieve]
452.
Komada Y,
Zhou Y-W,
Zhang X-L,
Xue H-L,
Sakai H,
Tanaka S,
Sakatoku H,
Sakurai M:
Fas receptor (CD95)-mediated apoptosis is induced in leukemic cells entering G1B compartment of the cell cycle.
Blood
86:3848,
1995[Abstract/Free Full Text]
453.
Giordano M,
Danova M,
Mazzini G,
Gobbi P,
Riccardi A:
Cell kinetics with in vivo bromodeoxyuridine assay, proliferating cell nuclear antigen expression, and flow cytometric analysis. Prognostic significance in acute nonlymphoblastic leukemia.
Cancer
71:2739,
1993[Medline]
[Order article via Infotrieve]
454.
Hiddemann W,
Harbott J,
Ludwig WD,
Ritter J,
Nehmer A,
Reiter A,
Kolkmeyer A,
Laing T,
Riehm H:
DNA aneuploidy in childhood acute lymphoblastic leukemia: Relation to clinical determinants and prognosis within four consecutive BFM trials.
Recent Result Cancer Res
131:113,
1993[Medline]
[Order article via Infotrieve]
455.
Look AT,
Roberson PK,
William DL,
Rivera G,
Bowman WP,
Pui CH,
Ochs J,
Abromowitch M,
Kalwinsky D,
Dahl GV:
Prognostic importance of blast cell DNA content in childhood acute lymphoblastic leukemia.
Blood
65:1079,
1985[Abstract/Free Full Text]
456.
Carbonari M,
Cibati M,
Fiorilli M:
Measurement of apoptotic cells in peripheral blood.
Cytometry
22:161,
1995[Medline]
[Order article via Infotrieve]
457.
Chiu L,
Cherwinski H,
Ransom J,
Dunne JF:
Ratiometric Hoescht 33342 emission analysis allows multiparametric characterization of apoptotic lymphocytes.
J Immunol Methods
189:157,
1995
458.
Martin SJ,
Reutelingsperger CPM,
McGahon AJ,
Rader JA,
Van Schie RCAA,
LaFace DM,
Green DR:
Early redistribution of plasma membrane phosphatidylserine is a general feature of apoptosis regardless of the initiating stimulus: Inhibition by overexpression of Bcl-2 and Ab1.
J Exp Med
182:1545,
1995[Abstract/Free Full Text]
459.
Vermes I,
Haanen C,
Steffens-Nakken H,
Reutelingsperger C:
A novel assay for apoptosis flow cytometric detection of phosphatidylserine expression on early apoptotic cells using fluorescein labelled annexin V.
J Immunol Methods
184:39,
1995[Medline]
[Order article via Infotrieve]
460.
Reid S,
Cross R,
Snow EC:
Combined Hoechst 33342 and merocyanine 540 staining to examine murine B cell cycle stage, viability and apoptosis.
J Immunol Methods
192:43,
1996[Medline]
[Order article via Infotrieve]
 CiteULike  Connotea  Del.icio.us  Digg  Reddit  Technorati What's this?
This article has been cited by other articles:
|
|
|
|
 
M. C. Bene and J. S. Kaeda
How and why minimal residual disease studies are necessary in leukemia: a review from WP10 and WP12 of the European LeukaemiaNet
Haematologica,
August 1, 2009;
94(8):
1135 - 1150.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
X.-Q. Xu, J.-M. Wang, S.-Q. Lu, L. Chen, J.-M. Yang, W.-P. Zhang, X.-M. Song, J. Hou, X. Ni, and H.-Y. Qiu
Clinical and biological characteristics of adult biphenotypic acute leukemia in comparison with that of acute myeloid leukemia and acute lymphoblastic leukemia: a case series of a Chinese population
Haematologica,
July 1, 2009;
94(7):
919 - 927.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. Al-Mawali, D. Gillis, and I. Lewis
The Role of Multiparameter Flow Cytometry for Detection of Minimal Residual Disease in Acute Myeloid Leukemia
Am J Clin Pathol,
January 1, 2009;
131(1):
16 - 26.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
F. E. Craig and K. A. Foon
Flow cytometric immunophenotyping for hematologic neoplasms
Blood,
April 15, 2008;
111(8):
3941 - 3967.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
G. Fazio, C. Palmi, A. Rolink, A. Biondi, and G. Cazzaniga
PAX5/TEL Acts as a Transcriptional Repressor Causing Down-modulation of CD19, Enhances Migration to CXCL12, and Confers Survival Advantage in pre-BI Cells
Cancer Res.,
January 1, 2008;
68(1):
181 - 189.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
E.-Q. Song, G.-P. Wang, H.-Y. Xie, Z.-L. Zhang, J. Hu, J. Peng, D.-C. Wu, Y.-B. Shi, and D.-W. Pang
Visual Recognition and Efficient Isolation of Apoptotic Cells with Fluorescent-Magnetic-Biotargeting Multifunctional Nanospheres
Clin. Chem.,
December 1, 2007;
53(12):
2177 - 2185.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
P. Venugopal and S. A. Gregory
Lymphoproliferative disorders
ASH Self-Assessment Program,
January 1, 2007;
2007(1):
265 - 297.
[Full Text]
[PDF]
|
|
|
|
|
|
|
H. Abe and E. T. Kool
Flow cytometric detection of specific RNAs in native human cells with quenched autoligating FRET probes
PNAS,
January 10, 2006;
103(2):
263 - 268.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
W. Janni, B. Rack, K. Lindemann, and N. Harbeck
Detection of Micrometastatic Disease in Bone Marrow: Is It Ready for Prime Time?
Oncologist,
August 1, 2005;
10(7):
480 - 492.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
L.-I. Lin, C.-Y. Chen, D.-T. Lin, W. Tsay, J.-L. Tang, Y.-C. Yeh, H.-L. Shen, F.-H. Su, M. Yao, S.-Y. Huang, et al.
Characterization of CEBPA Mutations in Acute Myeloid Leukemia: Most Patients with CEBPA Mutations Have Biallelic Mutations and Show a Distinct Immunophenotype of the Leukemic Cells
Clin. Cancer Res.,
February 15, 2005;
11(4):
1372 - 1379.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
I. C. Nicholson, M. Ayhan, N. J. Hoogenraad, and H. Zola
In silico evaluation of two mass spectrometry-based approaches for the identification of novel human leukocyte cell-surface proteins
J. Leukoc. Biol.,
February 1, 2005;
77(2):
190 - 198.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. T. Hehn, T. M. Grogan, and T. P. Miller
Utility of Fine-Needle Aspiration As a Diagnostic Technique in Lymphoma
J. Clin. Oncol.,
August 1, 2004;
22(15):
3046 - 3052.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. Shiohara, A. F. Gombart, Y. Sekiguchi, E. Hidaka, S. Ito, T. Yamazaki, H. P. Koeffler, and A. Komiyama
Phenotypic and functional alterations of peripheral blood monocytes in neutrophil-specific granule deficiency
J. Leukoc. Biol.,
February 1, 2004;
75(2):
190 - 197.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
T. Ikeda, Y. Nakata, F. Kimura, K. Sato, K. Anderson, K. Motoyoshi, M. Sporn, and D. Kufe
Induction of redox imbalance and apoptosis in multiple myeloma cells by the novel triterpenoid 2-cyano-3,12-dioxoolean-1,9-dien-28-oic acid
Mol. Cancer Ther.,
January 1, 2004;
3(1):
39 - 45.
[Abstract]
[Full Text]
|
|
|
|
|
|
|
J. McCafferty-Grad, N. J. Bahlis, N. Krett, T. M. Aguilar, I. Reis, K. P. Lee, and L. H. Boise
Arsenic trioxide uses caspase-dependent and caspase-independent death pathways in myeloma cells
Mol. Cancer Ther.,
November 1, 2003;
2(11):
1155 - 1164.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
E. Sanz, M. Alvarez-Mon, C. Martinez-A, and A. de la Hera
Human cord blood CD34+Pax-5+ B-cell progenitors: single-cell analyses of their gene expression profiles
Blood,
May 1, 2003;
101(9):
3424 - 3430.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. Ruzickova, A. Pruss, M. Odendahl, K. Wolbart, G.-R. Burmester, J. Scholze, T. Dorner, and A. Hansen
Chronic lymphocytic leukemia preceded by cold agglutinin disease: intraclonal immunoglobulin light-chain diversity in VH4-34 expressing single leukemic B cells
Blood,
October 16, 2002;
100(9):
3419 - 3422.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. M. Grad, N. J. Bahlis, I. Reis, M. M. Oshiro, W. S. Dalton, and L. H. Boise
Ascorbic acid enhances arsenic trioxide-induced cytotoxicity in multiple myeloma cells
Blood,
August 1, 2001;
98(3):
805 - 813.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. C. Rawstron, B. Kennedy, P. A. S. Evans, F. E. Davies, S. J. Richards, A. P. Haynes, N. H. Russell, G. Hale, G. J. Morgan, A. S. Jack, et al.
Quantitation of minimal disease levels in chronic lymphocytic leukemia using a sensitive flow cytometric assay improves the prediction of outcome and can be used to optimize therapy
Blood,
July 1, 2001;
98(1):
29 - 35.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
D. L. Jaye, H. A. Edens, L. Mazzucchelli, and C. A. Parkos
Novel G Protein-Coupled Responses in Leukocytes Elicited by a Chemotactic Bacteriophage Displaying a Cell Type-Selective Binding Peptide
J. Immunol.,
June 15, 2001;
166(12):
7250 - 7259.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
L. Belov, O. de la Vega, C. G. dos Remedios, S. P. Mulligan, and R. I. Christopherson
Immunophenotyping of Leukemias Using a Cluster of Differentiation Antibody Microarray
Cancer Res.,
June 1, 2001;
61(11):
4483 - 4489.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
Y. Kee Shin, E. Young Choi, S. Hyung Kim, J. Chung, D. Hyun Chung, W. Seo Park, K. Cheon Jung, H. Sik Kim, S. Park, H. Jin Kim, et al.
Expression of Leukemia-Associated Antigen, JL1, in Bone Marrow and Thymus
Am. J. Pathol.,
April 1, 2001;
158(4):
1473 - 1480.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. Brown and C. Wittwer
Flow Cytometry: Principles and Clinical Applications in Hematology
Clin. Chem.,
August 1, 2000;
46(8):
1221 - 1229.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
I. Tinhofer, I. Marschitz, T. Henn, A. Egle, and R. Greil
Expression of functional interleukin-15 receptor and autocrine production of interleukin-15 as mechanisms of tumor propagation in multiple myeloma
Blood,
January 15, 2000;
95(2):
610 - 618.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
C. Palomo, X. Zou, I. C. Nicholson, C. Butzler, and M. Bruggemann
B-Cell Tumorigenesis in Mice Carrying a Yeast Artificial Chromosome-based Immunoglobulin Heavy/c-myc Translocus Is Independent of the Heavy Chain Intron Enhancer (E{micro})
Cancer Res.,
November 1, 1999;
59(21):
5625 - 5628.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. Orfao, G. Schmitz, B. Brando, A. Ruiz-Arguelles, G. Basso, R. Braylan, G. Rothe, F. Lacombe, F. Lanza, S. Papa, et al.
Clinically Useful Information Provided by the Flow Cytometric Immunophenotyping of Hematological Malignancies: Current Status and Future Directions
Clin. Chem.,
October 1, 1999;
45(10):
1708 - 1717.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
K. Pantel, R. J. Cote, and O. Fodstad
Detection and Clinical Importance of Micrometastatic Disease
J Natl Cancer Inst,
July 7, 1999;
91(13):
1113 - 1124.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. M. Oliver, F. Martin, and J. F. Kearney
IgMhighCD21high Lymphocytes Enriched in the Splenic Marginal Zone Generate Effector Cells More Rapidly Than the Bulk of Follicular B Cells
J. Immunol.,
June 15, 1999;
162(12):
7198 - 7207.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
K. Tsuganezawa, N. Kiyokawa, Y. Matsuo, F. Kitamura, N. Toyama-Sorimachi, K. Kuida, J. Fujimoto, and H. Karasuyama
Flow Cytometric Diagnosis of the Cell Lineage and Developmental Stage of Acute Lymphoblastic Leukemia by Novel Monoclonal Antibodies Specific to Human Pre-B-Cell Receptor
Blood,
December 1, 1998;
92(11):
4317 - 4324.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
R. Wasserman, X.-X. Zeng, and R. R. Hardy
The Evolution of B Precursor Leukemia in the Eľ-ret Mouse
Blood,
July 1, 1998;
92(1):
273 - 282.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. E. Rubnitz and C.-H. Pui
Childhood Acute Lymphoblastic Leukemia
Oncologist,
December 1, 1997;
2(6):
374 - 380.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
Introduction
References
Introduction