Thrombopoietin responsiveness reflects the number of doublings undergone by megakaryocyte progenitors.

Thrombopoietin Responsiveness Reflects the Number of Doublings Undergone by Megakaryocyte Progenitors Short Title : Tpo Responsiveness of Megakaryocyte Progenitors

Phosphatidylinositol 3-kinase is necessary but not sufficient for thrombopoietin-induced proliferation in engineered Mpl-bearing cell lines as well as in primary megakaryocytic progenitors.

Thrombopoietin and its receptor (Mpl) support survival and proliferation in megakaryocyte progenitors and in BaF3 cells engineered to stably express Mpl (BaF3/Mpl). The binding of thrombopoietin to Mpl activates multiple kinase pathways, including the Jak/STAT, Ras/Raf/MAPK, and phosphatidylinositol 3-kinase pathways, but it is not clear how these kinases promote cell cycling. Here, we show tha...

Thrombopoietin: biology and potential clinical applications.

After an almost 40-year search for a primary regulatory of platelet production, thrombopoietin has recently been purified and cloned. Thrombopoietin regulates all stages in the production of platelets by promoting both the proliferation of megakaryocyte progenitors and their maturation into platelet-producing megakaryocytes. In preclinical studies in normal mice and non-human primates, administ...

Anomalous megakaryocytopoiesis in mice with mutations in the c-Myb gene.

Mpl(-/-) mice bearing the Plt3 or Plt4 mutations in the c-Myb gene exhibit thrombopoietin (TPO)-independent supraphysiological platelet production accompanied by excessive megakaryocytopoiesis and defective erythroid and lymphoid cell production. To better define the cellular basis for the thrombocytosis in these mice, we analyzed the production and characteristics of megakaryocytes and their p...

Thrombopoietin, but not erythropoietin promotes viability and inhibits apoptosis of multipotent murine hematopoietic progenitor cells in vitro.

The recently cloned c-mpl ligand, thrombopoietin (Tpo), has been extensively characterized with regard to its ability to stimulate the growth, development, and ploidy of megakaryocyte progenitor cells and platelet production in vitro and in vivo. Primitive hematopoietic progenitors have been shown to express c-mpl, the receptor for Tpo. In the present study, we show that Tpo efficiently promote...