Effects of the leukemia-associated AML1-ETO protein on hematopoietic stem and progenitor cells.
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 myelogenous 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.
Nimer
Stephen D
SD
Laboratory of Molecular Aspects of Hematopoiesis, Sloan-Kettering Institute, Memorial Sloan-Kettering Cancer Center, New York, NY 10021, USA. s-nimer@mskcc.org
Moore
Malcolm A S
MA
D050676:Core Binding Factor Alpha 2 Subunit; D006412:Hematopoietic Stem Cells / Q000378:metabolism*; D006801:Humans; D007938:Leukemia / Q000235:genetics / Q000378:metabolism; D015514:Oncogene Proteins, Fusion / Q000235:genetics* / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D000075142:RUNX1 Translocation Partner 1 Protein; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism
C107844:AML1-ETO fusion protein, human; D050676:Core Binding Factor Alpha 2 Subunit; D015514:Oncogene Proteins, Fusion; D012333:RNA, Messenger; D000075142:RUNX1 Translocation Partner 1 Protein; D014157:Transcription Factors