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Acute Leukemia Forum 2000, Advances and Controversies in the Therapy of Acute Myelogenous Leukemia

AML1/CBFβ transcription complex: its role in normal hematopoiesis and leukemia

Leukemia volume 15, pages 664–665 (2001)Cite this article

Acute myelogenous leukemia (AML) is a heterogeneous disease that is classified based on the morphology of the blasts and by the presence or absence of specific cytogenetic abnormalities. Two of the more common cytogenetic abnormalities, t(8;21) and inv(16), are seen in cases with different morphologies; however, recent studies have revealed that they have a common underlying pathogenesis and are therefore referred to collectively as the core binding factor leukemias (reviewed in Downing). These translocations result in the alteration of the genes that encode the AML1/CBFβ core binding factor transcription complex, a critical regulator of normal hematopoiesis.

AML1 was initially identified as the target of the t(8;21) and was shown to encode a transcription factor that contained a central domain of approximately 100 amino acids that has a very high level of homology to the Drosophila pair-rules protein runt. AML1 binds to the core enhancer DNA sequence, TGT/GGT, through its central runt homology domain (RHD) and its affinity for DNA is increased by heterodimerization through the RHD with a second subunit called CBFβ. This heterodimeric transcription factor regulates the transcription of a large number of hematopoietic-specific targets, including but not limited to myeloperoxidase, CSF1 receptor, the subunits of the T cell antigen receptor, interleukin (IL)-3, and GM-CSF.

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  1. Department of Pathology, St Jude Children's Research Hospital, 332 North Lauderdale Street, Memphis, TN 38105, USA

    JR Downing

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Downing, J. AML1/CBFβ transcription complex: its role in normal hematopoiesis and leukemia. Leukemia 15, 664–665 (2001). https://doi.org/10.1038/sj.leu.2402035

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