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Thrombopoietin (TPO) is a glycoprotein hormone produced mainly by the liver and the kidney that regulates the production of platelets by the bone marrow. It stimulates the production and differentiation of megakaryocytes, the bone marrow cells that fragment into large numbers of plateletsKaushansky K. Lineage-specific hematopoietic growth factors. N Engl J Med 2006;354:2034-45. PMID 16687716..
Genetics
The thrombopoietin gene is located on the long arm of chromosome 3 (q26.3-27). Abnormalities in this gene occur in some hereditary forms of thrombocytosis (high platelet count) and in some cases of leukemia. Thrombopoietin shares its first 153 amino acids with erythropoietin.
Function and regulation
It is produced by the liver and kidney, as well as striated muscle and stromal cells in the bone marrow. In the liver, its production is augmented by interleukin 6 (IL-6).
Thrombopoietin regulates the differentiation of megakaryocytes and platelets, but studies on the removal of the thrombopoeitin receptor show that its effects on hematopoiesis are more versatile.
Its negative feedback is different from most hormones in endocrinology: the effector regulates the hormone directly. Thrombopoeitin is bound to the surface of platelets, thereby reducing megakaryocyte exposure to the hormone.
Therapeutic use
Despite numerous trials, thrombopoeitin is not used therapeutically. Theoretical uses include the procurement of platelets for donationKuter DJ, Goodnough LT, Romo J, DiPersio J, Peterson R, Tomita D, Sheridan W, McCullough J. Thrombopoietin therapy increases platelet yields in healthy platelet donors. Blood 2001;98:1339-45. Fulltext. PMID: 11520780., recovery of platelet counts after myelosuppressive chemotherapy.
A modified recombinant form, termed "megakaryocyte growth and differentiation factor" (MGDF), caused a paradoxical reaction, delaying the development of therapeutic thrombopoietin. A quadrivalent peptide analogue is undergoing development, as well as several small molecule agents.
A non-peptide ligand of c-Mpl, which acts as a thrombopoietin analogue, is under investigationNakamura T, Miyakawa Y, Miyamura A, Yamane A, Suzuki H, Ito M, Ohnishi Y, Ishiwata N, Ikeda Y, Tsuruzoe N. A novel non-peptidyl human c-Mpl activator stimulates human megakaryopoiesis and thrombopoiesis. Blood 2006;107:4300-7. PMID 16484588.
History
Thrombopoietin was cloned by five independent groups in 1994. Before its identification, its function has been hypothesized for as much as 30 years as being linked to the cell surface receptor c-Mpl, and in older publications thrombopoietin is described as c-Mpl ligand (the agent that binds to the c-Mpl molecule). Thrombopoietin is one of the Class I hematopoietic cytokines.
References
External links
"Thrombopoietin"