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DNA microarray analysis of hematopoietic stem cell-like fractions from individuals with the M2 subtype of acute myeloid leukemia

Abstract

Acute myeloid leukemia (AML) may develop de novo or secondarily to myelodysplastic syndrome (MDS). Although the clinical outcome of MDS-related AML is worse than that of de novo AML, it is not easy to differentiate between these two clinical courses without a record of prior MDS. Large-scale profiling of gene expression by DNA microarray analysis is a promising approach with which to identify molecular markers specific to de novo or MDS-related AML. This approach has now been adopted with AC133-positive hematopoietic stem cell-like fractions purified from 10 individuals, each with either de novo or MDS-related AML of the M2 subtype. Sets of genes whose activity was associated with either disease course were identified. Furthermore, on the basis of the expression profiles of these genes, it was possible to predict correctly the clinical diagnosis for 17 (85%) of the 20 cases in a cross-validation trial. Similarly, different sets of genes were identified whose expression level was associated with clinical outcome after induction chemotherapy. These data suggest that, at least in terms of gene expression profiles, de novo AML and MDS-related AML are distinct clinical entities.

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Acknowledgements

We thank all the physicians and patients who participated in the collection of Blast Bank samples. This work was supported in part by grants for Research on the Human Genome, Tissue Engineering, and Food Biotechnology, for the Second-Term Comprehensive 10-Year Strategy for Cancer Control, and for Research on Development of Novel Therapeutic Modalities for Myelodysplastic Syndrome from the Ministry of Health, Labor, and Welfare of Japan; by the Science Research Promotion Fund of the Promotion and Mutual Aid Corporation for Private Schools of Japan; by a grant from Research Foundation for Community Medicine of Japan; by a grant from Sankyo Foundation of Life Science; and by a grant from Takeda Science Foundation. JO is a research resident of the Japan Health Sciences Foundation.

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Oshima, Y., Ueda, M., Yamashita, Y. et al. DNA microarray analysis of hematopoietic stem cell-like fractions from individuals with the M2 subtype of acute myeloid leukemia. Leukemia 17, 1990–1997 (2003). https://doi.org/10.1038/sj.leu.2403098

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