ONCOPROTEIN E2A-PBX1 IMMORTALIZES A MYELOID PROGENITOR IN PRIMARY MARROW CULTURES WITHOUT ABROGATING ITS FACTOR-DEPENDENCE

E2A-PBX1 is a chimeric homeobox oncogene formed by the t(1;19) translo cation of human pre-B cell acute lymphoblastic leukemia (ALL). Tn a pr evious study, we found that retroviral expression of E2A-Phx1 in the m arrow of reconstituted mice induced the formation of acute myeloid leu kemia (AML) in vivo. Here, we report that E2A-Pbx1 can also immortaliz e myeloid progenitors in vitro, and that the outgrowth of immortalized myeloblasts is evident only in the presence of the myeloid lymphokine , granulocyte-macrophage colony stimulating factor (GM-CSF). When cult ured in the presence of GM-CSP, responsive myeloblasts from normal mar row exhibit concurrent proliferation and differentiation, and undergo terminal differentiation into non-mitotic neutrophils and macrophages within 4 weeks. Infection of identical cultures with a retrovirus enco ding E2A-Pbx1 produces a rapid outgrowth of myeloid progenitors that e xpress high levels of E2A-Pbx1 protein. A small fraction of myeloblast s in each population exhibited limited differentiation to neutrophils, and all populations of myeloblasts retained a strict dependence on GM -CSF for both survival and proliferation. This data suggests that the function of E2A-Pbx1 in leukemias is to strongly retard differentiatio n without affecting growth-factor dependence.