The genetic defects underlying the pathogenesis of acute myeloid leukemia
(AML) are still largely unknown. Retroviral insertion mutagenesis in mice
has become a powerful tool to identify candidate genes involved in the
development of leukemia and lymphoma. We have used this strategy with the
1.4 strain of Graffi murine leukemia virus (MuLV), which predominantly
causes myeloid leukemias. Here, we report that Graffi-1.4-induced AML
frequently harbors virus integrations in the gene encoding the
transcription factor Yin Yang 1 (YY1). These integrations occurred in both
orientations, and all were located in the 5' promoter region of the gene,
0.5 to 1.5 kb upstream of the major transcriptional start site. Luciferase
reporter assays showed