|
|
 Previous Article | Table of Contents | Next Article 
Blood, Vol. 94 No. 10 (November 15), 1999:
pp. 3509-3515
Lymphomas Expressing ALK Fusion Protein(s) Other Than NPM-ALK
Brunangelo Falini,
Karen Pulford,
Alessandra Pucciarini,
Antonino Carbone,
Chris De Wolf-Peeters,
Jacqueline Cordell,
Marco Fizzotti,
Antonella Santucci,
Pier-Giuseppe Pelicci,
Stefano Pileri,
Elias Campo,
German Ott,
Georges Delsol, and
David Y. Mason
From the Institutes of Hematology and Internal Medicine, University
of Perugia, Perugia, Italy; the LRF Immunodiagnostics Unit, John
Radcliffe Hospital, Oxford, UK; the Division of Pathology, Oncology
Reference Center, National Tumor Institute, Aviano, Italy; the
Institute of Pathology, University of Leuven, Leuven, Belgium; the
European Oncology Institute, Milan, Italy; the Institute of Pathology,
University of Bologna, Bologna, Italy; the Laboratory of Pathology,
Hospital Clinic, University of Barcelona, Barcelona, Spain; the
Department of Pathology, University of Würzburg, Würzburg,
Germany; the Laboratory of Anatomic Pathology, Hospital of Toulouse,
C.H.U. Purpan, Toulouse, France.
The tumor cells in ALK-positive lymphoma ("ALKoma") usually
express the product of the NPM-ALK chimeric gene, generated by the t(2;5) chromosomal translocation. However, 10% to 20% of
ALK-positive lymphomas express ALK fusion protein(s) other than
NPM-ALK, and in this report, we describe the immunohistologic and
clinicopathologic features of 15 such cases. The absence of the
NPM-ALK fusion gene was confirmed by reverse
transcriptase-polymerase chain reaction (RT-PCR) in 8 cases and by
fluorescence in situ hybridization (FISH) analysis in a
further 2 cases. In each case, ALK staining was restricted to the
cytoplasm and the N-terminus of NPM to the nucleus (contrasting with
lymphomas expressing NPM-ALK in which cytoplasmic as well as nuclear
labeling is seen). However, in the course of screening 53 ALK-positive
lymphomas, 2 biopsies were found that had a "cytoplasm-only" ALK
staining pattern but that nevertheless were shown to carry the (2;5)
(by NPM staining and RT-PCR). The 15 cases resembled typical
NPM-ALK-positive lymphomas in that all were of T or null phenotype,
usually occurred in young male patients, and frequently presented with
advanced disease associated with systemic symptoms and extranodal
involvement. Moreover, their prognosis was excellent and
indistinguishable from that of classical t(2;5)-positive tumors, but
was clearly different from that of ALK-negative anaplastic large-cell
lymphomas. These results suggest that lymphomas carrying variants of
the NPM-ALK fusion protein can be detected by immunostaining for ALK and NPM and also that they can be grouped with classical
t(2;5)-positive tumors as a single entity (ALK-positive lymphoma or
"ALKoma") that shows a better prognosis than ALK-negative
anaplastic large-cell lymphoma.
 CiteULike  Connotea  Del.icio.us  Digg  Reddit  Technorati What's this?
This article has been cited by other articles:
|
|
|
|
 
B. Falini and M. P. Martelli
Anaplastic large cell lymphoma: changes in the World Health Organization classification and perspectives for targeted therapy
Haematologica,
July 1, 2009;
94(7):
897 - 900.
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. P. Martelli, G. Sozzi, L. Hernandez, V. Pettirossi, A. Navarro, D. Conte, P. Gasparini, F. Perrone, P. Modena, U. Pastorino, et al.
EML4-ALK Rearrangement in Non-Small Cell Lung Cancer and Non-Tumor Lung Tissues
Am. J. Pathol.,
February 1, 2009;
174(2):
661 - 670.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. K. C. Chan, L. Lamant, E. Algar, G. Delsol, W. Y. W. Tsang, K. C. Lee, K. Tiedemann, and C. W. Chow
ALK+ histiocytosis: a novel type of systemic histiocytic proliferative disorder of early infancy
Blood,
October 1, 2008;
112(7):
2965 - 2968.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
H. M. Amin and R. Lai
Pathobiology of ALK+ anaplastic large-cell lymphoma
Blood,
October 1, 2007;
110(7):
2259 - 2267.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
B. Falini, I. Nicoletti, N. Bolli, M. P. Martelli, A. Liso, P. Gorello, F. Mandelli, C. Mecucci, and M. F. Martelli
Translocations and mutations involving the nucleophosmin (NPM1) gene in lymphomas and leukemias
Haematologica,
April 1, 2007;
92(4):
519 - 532.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
B. Falini, I. Nicoletti, M. F. Martelli, and C. Mecucci
Acute myeloid leukemia carrying cytoplasmic/mutated nucleophosmin (NPMc+ AML): biologic and clinical features
Blood,
February 1, 2007;
109(3):
874 - 885.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
F. Y.-Y. Hsu, P. B. Johnston, K. A. Burke, and Y. Zhao
The Expression of CD30 in Anaplastic Large Cell Lymphoma Is Regulated by Nucleophosmin-Anaplastic Lymphoma Kinase-Mediated JunB Level in a Cell Type-Specific Manner.
Cancer Res.,
September 15, 2006;
66(18):
9002 - 9008.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
E. Jacobsen
Anaplastic Large-Cell Lymphoma, T-/Null-Cell Type
Oncologist,
July 1, 2006;
11(7):
831 - 840.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
B. Falini, N. Bolli, J. Shan, M. P. Martelli, A. Liso, A. Pucciarini, B. Bigerna, L. Pasqualucci, R. Mannucci, R. Rosati, et al.
Both carboxy-terminus NES motif and mutated tryptophan(s) are crucial for aberrant nuclear export of nucleophosmin leukemic mutants in NPMc+ AML
Blood,
June 1, 2006;
107(11):
4514 - 4523.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. A. Rizvi, A. M. Evens, M. S. Tallman, B. P. Nelson, and S. T. Rosen
T-cell non-Hodgkin lymphoma
Blood,
February 15, 2006;
107(4):
1255 - 1264.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
G. Cazzaniga, M. G. Dell'Oro, C. Mecucci, E. Giarin, R. Masetti, V. Rossi, F. Locatelli, M. F. Martelli, G. Basso, A. Pession, et al.
Nucleophosmin mutations in childhood acute myelogenous leukemia with normal karyotype
Blood,
August 15, 2005;
106(4):
1419 - 1422.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. Alcalay, E. Tiacci, R. Bergomas, B. Bigerna, E. Venturini, S. P. Minardi, N. Meani, D. Diverio, L. Bernard, L. Tizzoni, et al.
Acute myeloid leukemia bearing cytoplasmic nucleophosmin (NPMc+ AML) shows a distinct gene expression profile characterized by up-regulation of genes involved in stem-cell maintenance
Blood,
August 1, 2005;
106(3):
899 - 902.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
B. Falini, C. Mecucci, E. Tiacci, M. Alcalay, R. Rosati, L. Pasqualucci, R. La Starza, D. Diverio, E. Colombo, A. Santucci, et al.
Cytoplasmic Nucleophosmin in Acute Myelogenous Leukemia with a Normal Karyotype
N. Engl. J. Med.,
January 20, 2005;
352(3):
254 - 266.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
D. Cussac, C. Greenland, S. Roche, R.-Y. Bai, J. Duyster, S. W. Morris, G. Delsol, M. Allouche, and B. Payrastre
Nucleophosmin-anaplastic lymphoma kinase of anaplastic large-cell lymphoma recruits, activates, and uses pp60c-src to mediate its mitogenicity
Blood,
February 15, 2004;
103(4):
1464 - 1471.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
P. De Paepe, M. Baens, H. van Krieken, B. Verhasselt, M. Stul, A. Simons, B. Poppe, G. Laureys, P. Brons, P. Vandenberghe, et al.
ALK activation by the CLTC-ALK fusion is a recurrent event in large B-cell lymphoma
Blood,
October 1, 2003;
102(7):
2638 - 2641.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
T. Ouyang, R.-Y. Bai, F. Bassermann, C. von Klitzing, S. Klumpen, C. Miething, S. W. Morris, C. Peschel, and J. Duyster
Identification and Characterization of a Nuclear Interacting Partner of Anaplastic Lymphoma Kinase (NIPA)
J. Biol. Chem.,
August 8, 2003;
278(32):
30028 - 30036.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
N. S. Reading, S. D. Jenson, J. K. Smith, M. S. Lim, and K. S. J. Elenitoba-Johnson
5'-(RACE) Identification of Rare ALK Fusion Partner in Anaplastic Large Cell Lymphoma
J. Mol. Diagn.,
May 1, 2003;
5(2):
136 - 140.
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. L. Kutok and J. C. Aster
Molecular Biology of Anaplastic Lymphoma Kinase-Positive Anaplastic Large-Cell Lymphoma
J. Clin. Oncol.,
September 1, 2002;
20(17):
3691 - 3702.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. I. Martin-Subero, I. Chudoba, L. Harder, S. Gesk, W. Grote, F. J. Novo, M. J. Calasanz, and R. Siebert
Multicolor-FICTION: Expanding the Possibilities of Combined Morphologic, Immunophenotypic, and Genetic Single Cell Analyses
Am. J. Pathol.,
August 1, 2002;
161(2):
413 - 420.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
L. Hernandez, S. Bea, B. Bellosillo, M. Pinyol, B. Falini, A. Carbone, G. Ott, A. Rosenwald, A. Fernandez, K. Pulford, et al.
Diversity of Genomic Breakpoints in TFG-ALK Translocations in Anaplastic Large Cell Lymphomas : Identification of a New TFG-ALKXL Chimeric Gene with Transforming Activity
Am. J. Pathol.,
April 1, 2002;
160(4):
1487 - 1494.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
B. Falini and D. Y. Mason
Proteins encoded by genes involved in chromosomal alterations in lymphoma and leukemia: clinical value of their detection by immunocytochemistry
Blood,
January 15, 2002;
99(2):
409 - 426.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
Q. Zhang, P. N. Raghunath, L. Xue, M. Majewski, D. F. Carpentieri, N. Odum, S. Morris, T. Skorski, and M. A. Wasik
Multilevel Dysregulation of STAT3 Activation in Anaplastic Lymphoma Kinase-Positive T/Null-Cell Lymphoma
J. Immunol.,
January 1, 2002;
168(1):
466 - 474.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. P. Greer, M. C. Kinney, and T. P. Loughran Jr.
T Cell and NK Cell Lymphoproliferative Disorders
Hematology,
January 1, 2001;
2001(1):
259 - 281.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
R.-Y. Bai, T. Ouyang, C. Miething, S. W. Morris, C. Peschel, and J. Duyster
Nucleophosmin-anaplastic lymphoma kinase associated with anaplastic large-cell lymphoma activates the phosphatidylinositol 3-kinase/Akt antiapoptotic signaling pathway
Blood,
December 15, 2000;
96(13):
4319 - 4327.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
H. Stein, H.-D. Foss, H. Durkop, T. Marafioti, G. Delsol, K. Pulford, S. Pileri, and B. Falini
CD30+ anaplastic large cell lymphoma: a review of its histopathologic, genetic, and clinical features
Blood,
December 1, 2000;
96(12):
3681 - 3695.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
D. A. Arber
Molecular Diagnostic Approach to Non-Hodgkin's Lymphoma
J. Mol. Diagn.,
November 1, 2000;
2(4):
178 - 190.
[Full Text]
|
|
|
|
|
|
|
R. Suzuki, Y. Kagami, K. Takeuchi, M. Kami, M. Okamoto, R. Ichinohasama, N. Mori, M. Kojima, T. Yoshino, H. Yamabe, et al.
Prognostic significance of CD56 expression for ALK-positive and ALK-negative anaplastic large-cell lymphoma of T/null cell phenotype
Blood,
November 1, 2000;
96(9):
2993 - 3000.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. Ladanyi
Aberrant ALK Tyrosine Kinase Signaling : Different Cellular Lineages, Common Oncogenic Mechanisms?
Am. J. Pathol.,
August 1, 2000;
157(2):
341 - 345.
[Full Text]
[PDF]
|
|
|
|
|
|
|
B. Lawrence, A. Perez-Atayde, M. K. Hibbard, B. P. Rubin, P. Dal Cin, J. L. Pinkus, G. S. Pinkus, S. Xiao, E. S. Yi, C. D. M. Fletcher, et al.
TPM3-ALK and TPM4-ALK Oncogenes in Inflammatory Myofibroblastic Tumors
Am. J. Pathol.,
August 1, 2000;
157(2):
377 - 384.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
C. Touriol, C. Greenland, L. Lamant, K. Pulford, F. Bernard, T. Rousset, D. Y. Mason, and G. Delsol
Further demonstration of the diversity of chromosomal changes involving 2p23 in ALK-positive lymphoma: 2 cases expressing ALK kinase fused to CLTCL (clathrin chain polypeptide-like)
Blood,
May 15, 2000;
95(10):
3204 - 3207.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. K. C. Chan
The Perivascular Cuff of Large Lymphoid Cells: A Clue to Diagnosis of Anaplastic Large Cell Lymphoma
International Journal of Surgical Pathology,
April 1, 2000;
8(2):
153 - 156.
[Abstract]
[PDF]
|
|
|
|
|
|
|
M. Trinei, L. Lanfrancone, E. Campo, K. Pulford, D. Y. Mason, P.-G. Pelicci, and B. Falini
A New Variant Anaplastic Lymphoma Kinase (ALK)-Fusion Protein (ATIC-ALK) in a Case of ALK-positive Anaplastic Large Cell Lymphoma
Cancer Res.,
February 1, 2000;
60(4):
793 - 798.
[Abstract]
[Full Text]
|
|
|
|
|
