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This complex process occurs in specialized niches in the bone marrow where <jats:styled-content style=\"fixed-case\">MK<\/jats:styled-content>s align adjacent to vascular endothelial cells, form proplatelet projections and release platelets into the circulation. Thrombopoietin (<jats:styled-content style=\"fixed-case\">THPO<\/jats:styled-content>,<jats:styled-content style=\"fixed-case\"> TPO<\/jats:styled-content>) is the primary growth factor for the <jats:styled-content style=\"fixed-case\">MK<\/jats:styled-content> lineage and necessary at all stages of development. <jats:styled-content style=\"fixed-case\">THPO<\/jats:styled-content> is constitutively produced in the liver, and binds to <jats:styled-content style=\"fixed-case\">MPL<\/jats:styled-content> (c\u2010<jats:styled-content style=\"fixed-case\">M<\/jats:styled-content>pl) receptor on platelets and <jats:styled-content style=\"fixed-case\">MK<\/jats:styled-content>s. This activates a cascade of signalling molecules, which induce transcription factors to drive <jats:styled-content style=\"fixed-case\">MK<\/jats:styled-content> development and thrombopoiesis. Decreased turnover rate and platelet number result in increased levels of free <jats:styled-content style=\"fixed-case\">THPO<\/jats:styled-content>, which induces a concentration\u2010dependant compensatory response of marrow\u2010<jats:styled-content style=\"fixed-case\">MK<\/jats:styled-content>s to enhance platelet production. Newly developed thrombopoietic agents operating via <jats:styled-content style=\"fixed-case\">MPL<\/jats:styled-content> receptor facilitate platelet production in thrombocytopenic states, primarily immune thrombocytopenia. Other drugs are available for attenuating malignant thrombocytosis. Herein, we review the regulation of megakaryocytopoiesis and platelet production in normal and disease states, and the innovative drugs and therapeutic modalities to stimulate or decrease thrombopoiesis.<\/jats:p>","DOI":"10.1111\/bjh.12328","type":"journal-article","created":{"date-parts":[[2013,4,18]],"date-time":"2013-04-18T10:52:32Z","timestamp":1366282352000},"page":"778-793","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":94,"title":["Advances in megakaryocytopoiesis and thrombopoiesis: from bench to bedside"],"prefix":"10.1111","volume":"161","author":[{"given":"Varda R.","family":"Deutsch","sequence":"first","affiliation":[{"name":"The Haematology Institute Tel Aviv Sourasky Medical Centre Tel Aviv Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aaron","family":"Tomer","sequence":"additional","affiliation":[{"name":"The Haematology Institute Tel Aviv Sourasky Medical Centre Tel Aviv 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