Oncoprotein E2A-Pbx1 immortalizes a myeloid progenitor in primary marrow cultures without abrogating its...

E2A-PBX1 is a chimeric homeobox oncogene formed by the t(1;19) translocation of human pre-B cell acute lymphoblastic leukemia (ALL). In a previous study, we found that retroviral expression of E2A-Pbx1 in the marrow of reconstituted mice induced the formation of acute myeloid leukemia (AML) in vivo. Here, we report that E2A-Pbx1 can also immortalize 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 cultured in the presence of GM-CSF, responsive myeloblasts from normal marrow 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 encoding E2A-Pbx1 produces a rapid outgrowth of myeloid progenitors that express high levels of E2A-Pbx1 protein. A small fraction of myeloblasts 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 differentiation without affecting growth-factor dependence.