C-Myb As A Key Player In The Control Of Myeloid Cell Differentiation

c-Myb is required for definitive haemopoiesis and is expressed in immature proliferating haemopoietic cells. This includes the myeloid compartment, where c-Myb is strongly expressed in progenitor cells and is down regulated as they mature. c-Myb activity inhibits differentiation, promotes cellular proliferation and survival of myeloid progenitor cells. We review the known target genes and molecular mechanisms contributing to these phenomena. Beyond influencing myeloid differentiation through the control of progenitor cell proliferation and survival, c-Myb may also play a direct role in lineage choice. Leukaemic retroviruses containing different mutant versions of c-Myb transform different types of myeloid cells. These naturally selected mutants appear to represent distinct ‘frozen’ activity states of c-Myb that differ in their ability to associate with cofactors and to activate specific target genes, with important consequences for the differentiation choice between the granulocytic and monocytic lineages.