The Role of the AML1 Transcription Factor in Leukemogenesis

Abstract

Chromosomal translocations are one of the hallmarks of human leukemias. These structural abnormalities result in the generation of genetic mutations that play a direct role in the transformation of hematopoietic stem cells. Some of the most common targets of these chromosomal rearrangements are the genes that encode the AML1/CBFβ transcription factor complex. The AML1/CBFβ complex plays a critical role in normal hematopoiesis, controlling the initiation of a transcriptional cascade required for the formation of definitive hematopoietic stem cells. Understanding how alterations in the normal biologic activity of this transcription factor complex lead to the initiation of leukemia will provide critical insights in the molecular pathogenesis of this disease. These insights in turn are likely to lead to the development of more rational approaches to the treatment of acute leukemia. In this review, we will summarize our current understanding of the mechanisms by which alterations in the activity of AML1/CBFβ contribute to the development of leukemia.