Abstract
Efforts to isolate genes involved in chromosomal translocations have led to the identification of several candidate oncogenes. One of the most frequent targets of gene mutations in human leukemia is AML1 (acute myeloid leukemia 1; also called runt-related transcription factor 1 : RUNX1), which encodes the DNA-binding subunit of the heterodimering transcriptional factor complex ; core-binding factor (CBF, or polyomavirus enhancer-binding protein 2 : PEBP2). This transcription complex plays an essential role in establishing early definitive hematopoietic development as documented through gene-targeting experiments. Many translocation-associated AML1 fusion gene products have been shown to function in leukemogenesis, at least in part, by dominantly interfering with this AML1's normal function by in vitro and in vivo experiments. Careful clinical studies have revealed that inactivating genomic mutations of this gene also contribute to some type of leukemia. Furthermore, many projects are in progress to define the entire pathway of the AML1/CBFB leukemia as a multistep carcinogenesis, using animal models or clinical mass studies, or both. In this review, a current understanding of the molecular basis for AML1 actions in normal and leukemic hematopoiesis is discussed.
