DISREGULATION OF MYC EXPRESSION IN MURINE BONE-MARROW CELLS RESULTS IN AN INABILITY TO PROLIFERATE IN SUBOPTIMAL GROWTH-FACTOR AND AN INCREASED SENSITIVITY TO DNA-DAMAGE

Derivatives of the murine bone marrow-derived, IL-3-dependent cell lin e, BAFS, were isolated following recombinant retroviral infection whic h showed disregulated expression of human c-Myc oncoprotein. Such cell s entered apoptosis and lost viability more rapidly than parental BAFS cells when IL-3 was removed, c-Myc disregulation also resulted in an inability of BAF3 cells to survive in either sub-optimal concentration s of IL-3, or saturating concentrations of IL-4 and insulin-like growt h factor-1. Furthermore, BAF3 cells with disregulated c-Myc expression were more sensitive to the induction of apoptosis by DNA-damaging age nts. These effects of c-Myc disregulation could be inhibited by co-exp ression of the Bcl-2 oncoprotein. The implications of these data for t he transformation of haematopoietic cells by disregulation of Myc expr ession are discussed.