v-Myb suppresses phorbol ester- and modifies retinoic acid-induced differentiation of human promonocytic U937 cells.

The c-myb protooncogene as well as its transforming derivate, the v-myb oncogene code for transcription factors. They regulate transcription of specific target genes thus controlling proliferation, differentiation and apoptosis of hematopoietic cells. Up-regulation of the c-myb expression or rearrangement/amplification of the myb locus are often involved in leukemogenesis. Enforced myb expression blocks differentiation of various leukemic cell lines. Human promonocytes U937 can be induced to differentiate to monocyte/macrophage-like cells using phorbol esters or to granulocytes using retinoic acid. In order to investigate transforming capability of v-myb, we expressed the v-myb oncogene of avian myeloblastosis virus in U937 cells. We found that v-Myb efficiently suppressed formation of macrophages upon treatment with phorbol ester. Some features of granulocytic differentiation of retinoic acid-treated U937 cells were affected by the v-Myb protein as well. These results document that v-Myb is significantly involved in control of myeloid differentiation.