C-MYB PREVENTS TPA-INDUCED DIFFERENTIATION AND CELL-DEATH IN V-MYB TRANSFORMED MONOBLASTS

Myelomonocytic cells transformed by v-Myb or altered forms of c-Myb do not contain the full-length c-Myb protein found in most immature hema topoietic cells. To determine if c-Myb was a dominant inhibitor of v-M yb, we have induced the synthesis of full-length c-Myb in monoblasts t ransformed by v-Myb. We found that although some morphological changes occurred, the presence of both c-Myb and v-Myb was compatible with ce ll growth. However, the response to phorbol ester (TPA) was significan tly altered by c-Myb. Monoblasts transformed by v-Myb can be induced t o differentiate into macrophages by treatment with TPA. This process i s accompanied by a significant amount of cell death. However, when c-M yb was made TPA-inducible in these cells, TPA-induced differentiation into macrophages was blocked and cell death was prevented. These resul ts demonstrate a significant difference in the biological effects of v -Myb and c-Myb in transformed myelomonocytic cells.