ESTABLISHMENT OF MYELOID PROGENITOR LINES FROM PRIMARY CULTURES OF MURINE BONE-MARROW CELLS EXPRESSING A V-MYB ONCOPROTEIN

Infection of primary hematopoietic progenitors from post 5-fluorouracil-treated murine bone marrow with a novel replication-defective retroviral vector [murine stem cell virus-v-myb (MSCV-v-myb)] bearing a v-myb oncogene reproducibly gave rise to permanent myeloid cell lines that were dependent on either interleukin (LL)-3 or granulocyte-macrophage colony-stimulating factor (GM-CSF) for sustained growth in vitro. All of the v-Myb-transformed myeloid cells synthesized an apparently normal c-Myb protein in addition to the predicted v-Myb species, indicating that expression of c-Myb is not incompatible with transformation by v-Myb. Cell lines derived in the presence of GM-CSF proliferated maximally in response to this factor but also responded well to IL-3 and macrophage-CSF (M-CSF), and to a lesser extent to granulocyte-CSF (G-CSF) and Steel factor (SF). In contrast, v-Myb-transformed cell lines maintained in IL-3-supplemented medium were optimally stimulated by SF but, besides IL-3, did not respond to any of the other factors tested. Unlike the GM-CSF-dependent cell lines, these latter cell lines expressed the CD34 surface antigen that is present on a population of bone marrow cells with short- and long-term hematopoietic repopulating ability. To our knowledge, this is the first report documenting transformation of mammalian hematopoietic cells by v-Myb. The well-characterized murine hematopoietic system should prove valuable in further investigations aimed at elucidating the mechanisms by which ectopic v-Myb expression results in the immortalization of target cells belonging to varying stages of early myeloid development.