Thrombopoietin and the humoral regulation of thrombocytopoiesis

In 1994 four biotechnology research groups reported the isolation and cloning of the ligand for the cytokine receptor c-Mpl and showed it to be the long-sought regulator of platelet production, thrombopoietin. Thrombopoietin is a hematopoietic growth factor of 332 amino acids composed of an amino terminal domain homologous to erythropoietin and a highly glycosylated carboxyl domain. The erythropoietin-like domain is the functional domain, whereas the glycosylated domain appears to stabilize circulating thrombopoietin. Thrombopoietin stimulates both proliferation of progenitor megakaryocytes and their maturation to platelet-producing megakaryocytes. Thrombopoietin induces dramatic increases in megakaryocyte number and platelet production in mice, indicating that it regulates both thrombopoiesis and megakaryocytopoiesis. Thrombopoietin also accelerates the recovery of platelets in myelosuppressed animals, suggesting that it will be clinically useful for the treatment of thrombocytopenia.