Thrombopoietin Responsiveness Reflects the Number of Doublings Undergone by Megakaryocyte Progenitors Short Title : Tpo Responsiveness of Megakaryocyte Progenitors
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Thrombopoietin responsiveness reflects the number of doublings undergone by megakaryocyte progenitors.
To assess the variation of thrombopoietin (TPO) responsiveness associated with megakaryocyte (MK) progenitor amplification, TPO dose-response curves were obtained for normal human, single-cell plated CD34(+)CD41(+) cells. The number of MKs per well was determined in situ and expressed as number of doublings (NbD). Dose-response curves of the mean frequency of clones of each size versus log TPO ...
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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...
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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...
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