RT Book, Section A1 Kaushansky, Kenneth A2 Kaushansky, Kenneth A2 Lichtman, Marshall A. A2 Prchal, Josef T. A2 Levi, Marcel M. A2 Press, Oliver W. A2 Burns, Linda J. A2 Caligiuri, Michael SR Print(0) ID 1121101742 T1 Megakaryopoiesis and Thrombopoiesis T2 Williams Hematology, 9e YR 2015 FD 2015 PB McGraw-Hill Education PP New York, NY SN 9780071833004 LK hemonc.mhmedical.com/content.aspx?aid=1121101742 RD 2024/03/28 AB SUMMARYEach day the adult human produces approximately 1 × 1011 platelets, a level of production that can increase 10- to 20-fold in times of increased demand and an additional five- to 10-fold under the stimulation of exogenous thrombopoietin mimetic drugs. Production of platelets depends on the proliferation and differentiation of hematopoietic stem and progenitor cells to cells committed to the megakaryocyte lineage, their maturation to large, polyploid megakaryocytes, and their final fragmentation into platelets. The external influences that impact megakaryopoiesis and thrombopoiesis are a supportive marrow stroma consisting of endothelial and other cells, matrix glycosaminoglycans, and a family of protein hormones and cytokines, including thrombopoietin, stem cell factor, and stromal cell-derived factor-1. The role of the cytokines essential for these processes has been defined, the transcription factors critical for megakaryocyte development identified, the molecular mechanisms that underlie the two most unusual aspects of thrombopoiesis—endomitosis and proplatelet formation—have been studied, and reagents to specifically modify platelet production have been generated. This chapter focuses on the development of megakaryocytes, their precursors and their progeny, and the hematopoietic growth factors and transcriptionally active molecules that control the survival, proliferation, and differentiation of these cells.