Deregulated c-Myb expression in murine myeloid leukemias prevents the up-regulation of p15 INK4b normally associated with differentiation

Deregulated expression of the proto-oncogene c-myb, which results from provirus integration, is thought to be responsible for transformation in a set of murine leukemia virus (MuLV)-induced myeloid leukemias (MML). We reported recently that this transcription factor promotes proliferation by directly transactivating c-myc and inhibits cell death through its up-regulation of Bcl-2 (Schmidt et al., 2000). To understand more about how these cells become transformed we looked at how they deal with cellular pathways inducing growth arrest. Specifically, we were interested in the expression of the tumor suppressor gene Cdkn2b (p15 INK4b ) in MML because this gene is expressed during myeloid diAerentiation and its inactivation by methylation has been shown to be important for the development of human