Alterations of the AML1 transcription factor in human leukemia

The identification of clonal chromosomal translocations in human leukemias provided one of the first insights into the underlying pathogenesis of this clinically heterogeneous disease. Over the last decade a large number of these chromosomal rearrangements have been molecularly cloned and the involved genes identified. A surprising finding that has emerged from this work is that many of these chromosomal alterations target the genes encoding the AML1/CBFbeta transcription factor complex, a critical regulator of normal hematopoiesis. In this review, we summarize our present understanding of the mechanisms through which alterations of AML1/CBFbeta contribute to leukemogenesis.