THE GAG-MYB-ETS FUSION ONCOGENE ALTERS THE APOPTOTIC RESPONSE AND GROWTH-FACTOR DEPENDENCE OF INTERLEUKIN-3 DEPENDENT MURINE CELLS

Expression of the avian E26-derived Gag-Myb-Ets fusion oncogene in int erleukin-3(IL3)-dependent murine hematopoietic cell lines results in a pattern of cell line dependent changes in growth factor-induced proli feration and apoptosis. A drug-selectable retrovirus expressing p135(G ag-Myb-Ets) induced an erythropoietin(Epo)-responsive phenotype in the cell lines FDC-P2, BaF3 and 32Dc123. Gag-Myb-Ets expression alone did not increase expression of GATA-1 or the Epo receptor(EpoR) in the pr esence of IL3, and infected cell lines express increased GATA-1 and Ep oR only when IL3 was replaced by Epo in the culture media. Indicative of Epo-induced erythroid differentiation, these cells also began to ex press beta-globin after 3-5 days growth in Epo. Unlike control cells, infected FDC-P2 cells failed to undergo programmed cell death (apoptos is) when transferred from IL3- to Epo-containing media, although a fra ction of the cells failed to proliferate following the media shift. Th ree other IL3-dependent cell Lines showed no changes in growth behavio r when induced to express the fusion oncogene. Our data shows that Gag -Myb-Ets can have different affects on growth factor pathways dependin g on the cell background, suggesting a model in which the p135(gag-myb -ets) fusion oncogene promotes these different responses through its a ffect on apoptosis.