Abstract
Insights into the pathogenesis of human leukemia have relied heavily on studies of the identified chromosomal translocations found in this group of malignant diseases. Acquired, balanced translocations in acute myclogenous leukemia (AML) generally involve transcriptional regulatory genes, whereas in the myeloproliferative disorders tyrosine kinases are frequently involved. These rearrangements alter the function of at least one and often both of the involved genes. In this review, we focus on the AML1-ETO (a.k.a. RUNX1-ETO) fusion protein, which is found in t(8;21)+ AML. Expression of AML1-ETO in human hematopoietic stem cells (HSCs) preferentially enhances their maintenance, as opposed to their differentiation. The direct effects of AML1-ETO on human and murine HSCs, and the potentially cooperating events that may contribute to its leukemogenic properties, are discussed.
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Acknowledgements
This work was supported by a Leukemia, Lymphoma Society Specialized Center of Research Grant. We thank Ms Ellie Park for her assistance in the preparation of this paper. We also wish to express our profound sadness over the recent death of our friend, Dr Hisamaru Hirai, a leader in the laboratory and clinical investigation of leukemia and MDS.
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Nimer, S., Moore, M. Effects of the leukemia-associated AML1-ETO protein on hematopoietic stem and progenitor cells. Oncogene 23, 4249–4254 (2004). https://doi.org/10.1038/sj.onc.1207673
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DOI: https://doi.org/10.1038/sj.onc.1207673
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