Myeloid Progenitor Cells Transformed by the Myeloproliferative Leukemia Virus Proliferate and Differentiate in Vitro Without the Addition of Growth Factors

The myeloproliferative leukemia virus (MPLV) is an acute leukemogenic, nonsarcomatogenic replication-defective murine retrovirus which carries a novel oncogene, termed mpl. We recently reported that both late and early erythroid progenitors from MPLV-infected mice acquire erythropoietin and growth factor independence. In the present study, we show that MPLV-infected pluripotent, granulomacrophage and megakaryocyte progenitor cells proliferated and differentiated in semisolid cultures in the absence of the exogenous growth factors which are absolutely required for colony formation of normal hematopoietic progenitor cells. These factor-independent colonies were morphologically and cytologically similar to normal colonies and did not show any sign of impaired differentiation. Factor-independent colony formation was not influenced by the seeding density. MPLV-infected cells were unable to stimulate colony development of uninfected progenitors in coculture assays, and retransplanted clusters continued to grow in the absence of accessory cells. These data suggest that spontaneous colony formation does not result from a paracrine secretion of growth factors and indicate that MPLV is unique among naturally occurring murine retrovirus for its ability to abrogate the growth factor requirements of a broad spectrum of hematopoietic progenitor cells.