Factors involved in megakaryocyte development and platelet production

The processes of megakaryocytopoiesis and platelet production occur within a complex microenvironment where chemokines, cytokines and adhesive interactions play major roles. Megakaryocytopoiesis is regulated at several levels including proliferation, differentiation and platelet release. Thrombopoietin (TPO/c-Mpl ligand) is the most potent cytokine stimulating proliferation and maturation of MK progenitors but many other growth factors are involved. MK development is controlled by the action of multiple transcription factors. Many MK-specific genes are co-regulated by GATA and friend of GATA (FOG), RUNX1 and ETS proteins. Nuclear factor erythroid 2 (NF-E2), which has an MK-erythroid specific 45-kDa subunit, controls terminal MK maturation, proplatelet formation and platelet release. NF-E2 deficient mice have profound thrombocytopenia. MYB (c-myb) functions with EP300 (p300) as a negative regulator of thrombopoiesis. During MK maturation, internal membrane systems, granules and organelles are assembled. Cytoplasmic fragmentation requires changes in the MK cytoskeleton and formation of organelles and channels. Individual organelles migrate from the cell body to the proplatelet ends, with approximately 30 percent of organelles/granules in motion at any given time.