ROLE FOR C-MPL AND ITS LIGAND THROMBOPOIETIN IN EARLY HEMATOPOIESIS

Proto-oncogene c-mpl is structurally homologous with the hematopoietic growth factor receptor superfamily. The ligand for c-mpl was purified and its gene cloned, Extensive functional studies revealed that the l igand for c-mpl plays a crucial role in megakaryocytopoiesis and plate let production, hence, this ligand proved to be the long-sought hemato poietin, thrombopoietin (TPO), We briefly review here the role for TPO in early hematopoiesis, based on our in vitro data obtained using a s erum-free culture system. TPO in combination with the ligand for c-kit (SF) or interleukin-3 (IL-3) but not TPO alone supported the growth o f murine primitive hematopoietic progenitors, Studies on lineage expre ssion indicated that the progenitors supported by TPO plus SF or TPO p lus IL-3 are multipotential, Delayed addition experiments demonstrated that TPO has the potential to effectively support the survival of pri mitive hematopoietic progenitors, TPO also hastened IL-3-dependent gro wth of progenitors by shortening the time required for cell-cycling, W hile size of the colonies did not differ between colonies supported by IL-3 alone and those supported by IL-3 plus TPO, the incidence of meg akaryocyte-containing colonies in cultures supported by IL-3 plus TPO was higher than that in cultures supported by IL-3 alone. Taken togeth er, TPO as a single factor can support the survival of hematopoietic p rogenitors and TPO synergizes with SF or IL-3 to be active on early mu ltipotential hematopoietic progenitors. These findings suggest that th e function of TPO initially thought to be restricted to the megakaryoc ytic lineage proved to be greater in hematopoiesis. Reports from other laboratories regarding the involvement of TPO in early hematopoiesis are also discussed.