Molecular analysis of Evi1, a zinc finger oncogene involved in myeloid leukemia.

Through chromosomal rearrangements and/or proviral insertions, a number of genes encoding nuclear transcription factors have been identified that play key roles in leukemogenesis. One of these is Evi1, which plays a role in both murine and human myeloid leukemia. The exact mechanism by which Evi1 exerts its leukemogenic effect is not clear, but it may involve the inhibition of terminal differentiation, through the abnormal repression of genes necessary for cellular maturation. Our analysis of the DNA binding characteristics of EVI1 indicate a high degree of specificity, which likely indicates that the protein acts on a tightly defined number of targets in the cell. We are beginning to characterize candidate target genes located in the mouse genome near EVI1 binding sites with the expectation that these will yield insight into EVI1 function both in normal cells and in leukemogenesis.