title: Megakaryocyte development and platelet production.
abstract: Megakaryocytopoiesis involves the commitment of haematopoietic stem cells, and the proliferation, maturation and terminal differentiation of the megakaryocytic progenitors. Circulating levels of thrombopoietin (TPO), the primary growth-factor for the megakaryocyte (MK) lineage, induce concentration-dependent proliferation and maturation of MK progenitors by binding to the c-Mpl receptor and signalling induction. Decreased platelet turnover rates results in increased concentration of free TPO, enabling the compensatory response of marrow MKs to increased platelet production. C-Mpl activity is orchestrated by a complex cascade of signalling molecules that induces the action of specific transcription factors to drive MK proliferation and maturation. Mature MKs form proplatelet projections that are fragmented into circulating particles. Newly developed thrombopoietic agents operating via c-Mpl receptor may prove useful in supporting platelet production in thrombocytopenic state. Herein, we review the regulation of megakaryocytopoiesis and platelet production in normal and disease state, and the new approaches to thrombopoietic therapy.
authors.affiliation: The Haematology Institute, Tel Aviv Sourasky Medical Centre, Tel Aviv, Israel. varda@tasmc.health.gov.il
authors.forename: Varda R
authors.initials: VR
authors.lastname: Deutsch
authors.forename: Aaron
authors.initials: A
authors.lastname: Tomer
mesh_terms: D001792:Blood Platelets / Q000502:physiology*; D002454:Cell Differentiation; D049109:Cell Proliferation; D006410:Hematopoiesis / Q000502:physiology*; D006412:Hematopoietic Stem Cells / Q000166:cytology*; D006801:Humans; D008533:Megakaryocytes / Q000166:cytology*; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D018121:Receptors, Cytokine / Q000378:metabolism; D053628:Receptors, Thrombopoietin; D013921:Thrombocytopenia / Q000188:drug therapy; D013926:Thrombopoietin / Q000378:metabolism / Q000627:therapeutic use
chemical_list: D011518:Proto-Oncogene Proteins; D018121:Receptors, Cytokine; D053628:Receptors, Thrombopoietin; C082218:MPL protein, human; D013926:Thrombopoietin