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Evidence for malignant transformation in acute myeloid leukemia at the level of early hematopoietic stem cells by cytogenetic analysis of CD34+ subpopulations
Abstract
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.
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Citations
Cites
A cell initiating human acute myeloid leukaemia after transplantation into SCID mice
Lapidot, T., Sirard, C., Vormoor, J., Murdoch, B., Hoang, T., Caceres-Cortes, J., Minden, M., Paterson, B., Caligiuri, M. A., & Dick, J. E. (1994) · Nature · doi:10.1038/367645a0 · Cited by 4,783
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Bonnet, D., & Dick, J. E. (1997) · Nature Medicine · doi:10.1038/nm0797-730 · Cited by 5,864
Huntly, B. J. P., Shigematsu, H., Deguchi, K., Lee, B. H., Mizuno, S., Duclos, N., Rowan, R., Amaral, S., Curley, D., Williams, I. R., et al. (2004) · Cancer Cell · doi:10.1016/j.ccr.2004.10.015 · Cited by 697
Leukaemia stem cells and the evolution of cancer-stem-cell research
Huntly, B. J. P., & Gilliland, D. G. (2005) · Nature Reviews Cancer · doi:10.1038/nrc1592 · Cited by 483
Metadata
- Authors
- Haase, D., Feuring-Buske, M., Konemann, S., Fonatsch, C., Troff, C., Verbeek, W., Pekrun, A., Hiddemann, W., & Wormann, B.
- Venue
- Blood
- Publisher
- American Society of Hematology
- Published
- 1995-10-15
- Volume
- 86
- Issue
- 8
- Pages
- 2906-2912
- ISSN
- 0006-4971 (ISSN-L)
- 1528-0020
- OpenAlex
- W109176542
- Cited by
- 159
- References
- 1
- FWCI
- 5.35
- Type
- journal article
- Language
- en
- Open access
- closed
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- The paper
- Haase, D., Feuring-Buske, M., Konemann, S., Fonatsch, C., Troff, C., Verbeek, W., Pekrun, A., Hiddemann, W., & Wormann, B. (1995). Evidence for malignant transformation in acute myeloid leukemia at the level of early hematopoietic stem cells by cytogenetic analysis of CD34+ subpopulations. Blood. https://doi.org/10.1182/blood.v86.8.2906.2906
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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
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