2 Megakaryocyte function and dysfunction AMIRAM ELDOR ISRAEL VLODAVSKY VARDA DEUTSCH RICHARD F. LEVINE It has been known for 80 years that megakaryocytes are the progenitors of circulating platelets (Wright, 1906). These large nucleated cells develop in the bone marrow from multipotential stem cells and undergo differentiation and maturation which makes them capable of executing their main bio- logical function--the production of circulating platelets. In preparation for platelet production, megakaryocytes synthesize platelet proteins and assemble platelet organelles. The content of these platelet substances in megakaryocytes is comparable to that of platelets on a weight basis. Hence, megakaryocytes can be regarded as the compartment in which synthesis and progressive accumulation of platelet-specific materials occur. Platelets are end-stage cells which lack significant protein synthesis and may lose organelles as they undergo irreversible changes in the circulation. Platelet components may be modified in various diseases and clinical conditions, but the biosyntfietic origins of platelets are in megakaryocytes. Because megakaryocytes can be considered to be the immature form of platelets, important information on platelet composition and functional behaviour in various pathological processes can be gathered from studies on megakaryo- cytes. MEGAKARYOCYTE DIFFERENTIATION AND MATURATION Marrow multipotential stem cells develop into undifferentiated megakaryo- cytic, as well as erythroid and myeloid-monocytic precursors that pro- liferate in a clonal manner. The factors regulating the clonal proliferation of the undifferentiated megakaryocytes have been primarily determined in cultures of bone marrow progenitor cells. A growth stimulating factor, termed megakaryocyte colony-stimulating factor (meg-CSF), has been obtained from a variety of sources (Williams and Levine, 1982; Hoffman et al, 1985). In addition, a factor which augments the activity of meg-CSF has also been described (Williams et al, 1981, 1982), as well as interleukin-3 (Queensberry et al, 1985). The transition from undifferentiated but com- Bailli~re's Clinical Haematology--¥ol. 2, No. 3, J uly 1989 543