CHARACTERIZATION OF HUMAN MEGAKARYOCYTE CELL LINES

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Cells lines with properties of megakaryocytes have been established from the blood of normal donors and patients with myeloproliferative disorders. We request funds to fully characterize these lines. Furthermore, the susceptibility of the cultured megakaryocytes to infection with viruses will be fully investigated as to the mode of virus entry, replication and production in platelet precursor cells. The cell lines will be used to prepare monoclonal antibodies against selected megakaryocyte and/or platelet antigens. These reagents will be used (1) to identify the circulating precursor to megakaryocytes which is present in normal blood; (2) to recognize the megakaryoblast in leukemia cell preparations and (3) to study differentiation of these cell lines and short-term cultured cells towards fully mature megakaryocytes. The cell lines will offer the opportunity to study for the first time the synthesis of platelet glycoprotein IIb/IIIa and of fibrinogen in cells which are closely related to or are the same as megakaryocytes. The results of these studies will profoundly influence our understanding of megakaryocyte and platelet differentiation, just as the culture of T cells by the Principal Investigator has done. The proposal will generate cell lines of general interest to the scientific community. This proposal will also yield important monoclonal antibodies for the identification of megakaryocyte precursors among heterogeneous cell populations. Finally, the proposal will yield significant information into the physiology of megakaryocytopoiesis and into the pathophysiology of human congenital platelet defects.