|
|
 Previous Article | Table of Contents | Next Article 
Evidence for malignant transformation in acute myeloid leukemia at the
level of early hematopoietic stem cells by cytogenetic analysis of CD34+
subpopulations
D Haase, M Feuring-Buske, S Konemann, C Fonatsch, C Troff, W Verbeek, A Pekrun, W Hiddemann and B Wormann
Department of Hematology and Oncology, University of Gottingen, Germany.
Acute myeloid leukemia (AML) is a heterogenous disease according to
morphology, immunophenotype, and genetics. The retained capacity of
differentiation is the basis for the phenotypic classification of the bulk
population of leukemic blasts and the identification of distinct
subpopulations. Within the hierarchy of hematopoietic development and
differentiation it is still unknown at which stage the malignant
transformation occurs. It was our aim to analyze the potential involvement
of cells with the immunophenotype of pluripotent stem cells in the leukemic
process by the use of cytogenetic and cell sorting techniques. Cytogenetic
analyses of bone marrow aspirates were performed in 13 patients with AML
(11 de novo and 2 secondary) and showed karyotype abnormalities in 10 cases
[2q+, +4, 6p, t(6:9), 7, +8 in 1 patient each and inv(16) in 4 patients
each]. Aliquots of the samples were fractionated by fluorescence-activated
cell sorting of CD34+ cells. Two subpopulations, CD34+/CD38- (early
hematopoietic stem cells) and CD34+/CD38+ (more mature progenitor cells),
were screened for karyotype aberations as a marker for leukemic cells.
Clonal abnormalities and evaluable metaphases were found in 8 highly
purified CD34+/CD38- populations and in 9 of the CD34+/CD38- specimens,
respectively. In the majority of cases (CD34+/CD38-, 6 of 8 informative
samples; CD34+/CD38+, 5 of 9 informative samples), the highly purified
CD34+ specimens also contained cytogenetically normal cells. Secondary,
progression-associated chromosomal changes (+8, 12) were identified in the
CD34+/CD38- cells of 2 patients. We conclude that clonal karyotypic
abnormalities are frequently found in the stem cell-like (CD34+/CD38-) and
more mature (CD34+/CD38+) populations of patients with AML, irrespective of
the phenotype of the bulk population of leukemic blasts and of the primary
or secondary character of the leukemia. Our data suggest that, in AML,
malignant transformation as well as disease progression may occur at the
level of CD34+/CD38- cells with multilineage potential.
Volume 86,
Issue 8,
pp. 2906-2912,
10/15/1995
Copyright © 1995 by The American Society of Hematology
 CiteULike  Connotea  Del.icio.us  Digg  Reddit  Technorati What's this?
This article has been cited by other articles:
|
|
|
|
 
T. Nosslinger, H. Tuchler, U. Germing, W. R. Sperr, O. Krieger, D. Haase, M. Lubbert, R. Stauder, A. Giagounidis, P. Valent, et al.
Prognostic impact of age and gender in 897 untreated patients with primary myelodysplastic syndromes
Ann. Onc.,
July 15, 2009;
(2009)
mdp264v1.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
Y.-H. Kuo, R. M. Gerstein, and L. H. Castilla
Cbf{beta}-SMMHC impairs differentiation of common lymphoid progenitors and reveals an essential role for RUNX in early B-cell development
Blood,
February 1, 2008;
111(3):
1543 - 1551.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
D. Haase, U. Germing, J. Schanz, M. Pfeilstocker, T. Nosslinger, B. Hildebrandt, A. Kundgen, M. Lubbert, R. Kunzmann, A. A. N. Giagounidis, et al.
New insights into the prognostic impact of the karyotype in MDS and correlation with subtypes: evidence from a core dataset of 2124 patients
Blood,
December 15, 2007;
110(13):
4385 - 4395.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
T. Kawase, Y. Akatsuka, H. Torikai, S. Morishima, A. Oka, A. Tsujimura, M. Miyazaki, K. Tsujimura, K. Miyamura, S. Ogawa, et al.
Alternative splicing due to an intronic SNP in HMSD generates a novel minor histocompatibility antigen
Blood,
August 1, 2007;
110(3):
1055 - 1063.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
L. Zhao, J. L. Cannons, S. Anderson, M. Kirby, L. Xu, L. H. Castilla, P. L. Schwartzberg, R. Bosselut, and P. P. Liu
CBFB-MYH11 hinders early T-cell development and induces massive cell death in the thymus
Blood,
April 15, 2007;
109(8):
3432 - 3440.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
L. Pasqualucci, A. Liso, M. P. Martelli, N. Bolli, R. Pacini, A. Tabarrini, M. Carini, B. Bigerna, A. Pucciarini, R. Mannucci, et al.
Mutated nucleophosmin detects clonal multilineage involvement in acute myeloid leukemia: impact on WHO classification
Blood,
December 15, 2006;
108(13):
4146 - 4155.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. H.G.P. Raaijmakers, E. P.L.M. de Grouw, B. A. van der Reijden, T. J.M. de Witte, J. H. Jansen, and R. A.P. Raymakers
ABCB1 Modulation Does Not Circumvent Drug Extrusion from Primitive Leukemic Progenitor Cells and May Preferentially Target Residual Normal Cells in Acute Myelogenous Leukemia.
Clin. Cancer Res.,
June 1, 2006;
12(11):
3452 - 3458.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
H. Kawagoe and G. C. Grosveld
MN1-TEL myeloid oncoprotein expressed in multipotent progenitors perturbs both myeloid and lymphoid growth and causes T-lymphoid tumors in mice
Blood,
December 15, 2005;
106(13):
4278 - 4286.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. H.G.P. Raaijmakers, E. P.L.M. de Grouw, L. H.H. Heuver, B. A. van der Reijden, J. H. Jansen, R. J. Scheper, G. L. Scheffer, T. J.M. de Witte, and R. A.P. Raymakers
Breast Cancer Resistance Protein in Drug Resistance of Primitive CD34+38- Cells in Acute Myeloid Leukemia
Clin. Cancer Res.,
March 15, 2005;
11(6):
2436 - 2444.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
R. Gniadecki, A. Lukowsky, K. Rossen, H. O. Madsen, K. Thomsen, and H. C. Wulf
Bone marrow precursor of extranodal T-cell lymphoma
Blood,
November 15, 2003;
102(10):
3797 - 3799.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
Y. Guan, B. Gerhard, and D. E. Hogge
Detection, isolation, and stimulation of quiescent primitive leukemic progenitor cells from patients with acute myeloid leukemia (AML)
Blood,
April 15, 2003;
101(8):
3142 - 3149.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. G. Thomas, J. M. Olson, S. J. Tapscott, and L. P. Zhao
An Efficient and Robust Statistical Modeling Approach to Discover Differentially Expressed Genes Using Genomic Expression Profiles
Genome Res.,
July 1, 2001;
11(7):
1227 - 1236.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. Feuring-Buske and D. E. Hogge
Hoechst 33342 efflux identifies a subpopulation of cytogenetically normal CD34+CD38{-} progenitor cells from patients with acute myeloid leukemia
Blood,
June 15, 2001;
97(12):
3882 - 3889.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
L. Nilsson, I. Astrand-Grundstrom, I. Arvidsson, B. Jacobsson, E. Hellstrom-Lindberg, R. Hast, and S. E. W. Jacobsen
Isolation and characterization of hematopoietic progenitor/stem cells in 5q-deleted myelodysplastic syndromes: evidence for involvement at the hematopoietic stem cell level
Blood,
September 15, 2000;
96(6):
2012 - 2021.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
R. T. Costello, F. Mallet, B. Gaugler, D. Sainty, C. Arnoulet, J.-A. Gastaut, and D. Olive
Human Acute Myeloid Leukemia CD34+/CD38- Progenitor Cells Have Decreased Sensitivity to Chemotherapy and Fas-induced Apoptosis, Reduced Immunogenicity, and Impaired Dendritic Cell Transformation Capacities
Cancer Res.,
August 1, 2000;
60(16):
4403 - 4411.
[Abstract]
[Full Text]
|
|
|
|
|
|
|
E.L. Sievers, F.R. Appelbaum, R.T. Spielberger, S.J. Forman, D. Flowers, F.O. Smith, K. Shannon-Dorcy, M.S. Berger, and I.D. Bernstein
Selective Ablation of Acute Myeloid Leukemia Using Antibody-Targeted Chemotherapy: A Phase I Study of an Anti-CD33 Calicheamicin Immunoconjugate
Blood,
June 1, 1999;
93(11):
3678 - 3684.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. Blair, D.E. Hogge, and H.J. Sutherland
Most Acute Myeloid Leukemia Progenitor Cells With Long-Term Proliferative Ability In Vitro and In Vivo Have the Phenotype CD34+/CD71-/HLA-DR-
Blood,
December 1, 1998;
92(11):
4325 - 4335.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
N. Iijima, K. Miyamura, T. Itou, M. Tanimoto, R. Sobue, and H. Saito
Functional Expression of Fas (CD95) in Acute Myeloid Leukemia Cells in the Context of CD34 and CD38 Expression: Possible Correlation With Sensitivity to Chemotherapy
Blood,
December 15, 1997;
90(12):
4901 - 4909.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
B. Gahn, C. Schafer, J. Neef, C. Troff, M. Feuring-Buske, W. Hiddemann, and B. Wormann
Detection of Trisomy 12 and Rb-Deletion in CD34+ Cells of Patients With B-Cell Chronic Lymphocytic Leukemia
Blood,
June 15, 1997;
89(12):
4275 - 4281.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
