Thrombopoietin Receptor(TPO)/CD110, the main MK growth factor, is critical for normal MK proliferation and differentiation, and is a key initiator of thrombocytosis in many diseases. TPO is synthesized primarily in the liver as a 353 amino acid precursor protein with a molecular weight of 36 kDa TPO is expressed on early hematopoietic progenitors, megakaryocytes and platelets. Thrombopoietin (TPO) is the major physiological regulator of platelet production. The mechanism by which TPO binds to the TPO receptor and initiates signal transduction has been well outlined. Binding of TPO to its receptor initiates a wide variety of signal transduction pathways. The best known of these are the JAK and STAT pathways, which become phosphorylated and promote cell growth. In addition, MAP kinase pathways are activated, which potentiate maturation. TPO is necessary for the viability of stem cells, stimulates megakaryocyte endomitosis and increases the average ploidy of megakaryocytes, increases megakaryocyte maturation but seems to have little role in the release of platelets from megakaryocytes and affects early progenitor cells of other lineages.

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