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-fluorouraci l-treated murine bone marrow with a novel replication-defective retrov iral vector [murine stem cell virus-v-myb (MSCV-v-myb)] bearing a v-my b 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 norm al c-Myb protein in addition to the predicted v-Myb species, indicatin g that expression of c-Myb is not incompatible with transformation by v-Myb. Cell lines derived in the presence of GM-CSF proliferated maxim ally in response to this factor but also responded well to IL-3 and ma crophage-CSF (M-CSF), and to a lesser extent to granulocyte-CSF (G-CSF ) and Steel factor (SF). In contrast, v-Myb-transformed cell lines mai ntained in IL-3-supplemented medium were optimally stimulated by SF bu t, besides IL-3, did not respond to any of the other factors tested. U nlike the GM-CSF-dependent cell lines, these latter cell lines express ed the CD34 surface antigen that is present on a population of bone ma rrow cells with short- and long-term hematopoietic repopulating abilit y. To our knowledge, this is the first report documenting transformati on of mammalian hematopoietic cells by v-Myb. The well-characterized m urine hematopoietic system should prove valuable in further investigat ions aimed at elucidating the mechanisms by which ectopic v-Myb expres sion results in the immortalization of target cells belonging to varyi ng stages of early myeloid development.