[cite journal |author=Kaushansky K |title=Lineage-specific hematopoietic growth factors |journal=N. Engl. J. Med. |volume=354 |issue=19 |pages=2034–45 |year=2006 |pmid=16687716 |doi=10.1056/NEJMra052706] ] PBB_Summary
section_title =
summary_text = Megakaryocytopoiesis is the cellular development process that leads to platelet production. The protein encoded by this gene is a humoral growth factor that is necessary for megakaryocyte proliferation and maturation, as well as for thrombopoiesis. This protein is the ligand for MLP/C_MPL, the product of myeloproliferative leukemia virus oncogene.[cite web | title = Entrez Gene: THPO thrombopoietin (myeloproliferative leukemia virus oncogene ligand, megakaryocyte growth and development factor)| url = http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=7066| accessdate = ] ]
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. [OMIM|600044]
Function and regulation
In the liver it is produced by parenchymal cells and sinusoidal endothelial cells. In the kidney it is made by proximal convoluted tubule cells. Along with these it is made by 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 by the mpl receptor (CD 110) and destroyed, 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 donation [cite journal |author=Kuter DJ, Goodnough LT, Romo J, "et al" |title=Thrombopoietin therapy increases platelet yields in healthy platelet donors |journal=Blood |volume=98 |issue=5 |pages=1339–45 |year=2001 |pmid=11520780 |url=http://www.bloodjournal.org/cgi/content/full/98/5/1339 |doi=10.1182/blood.V98.5.1339] , 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,[ including several non-peptide ligands of "c-Mpl", which act as thrombopoietin analogues. [cite journal |author=Nakamura T, Miyakawa Y, Miyamura A, "et al" |title=A novel nonpeptidyl human c-Mpl activator stimulates human megakaryopoiesis and thrombopoiesis |journal=Blood |volume=107 |issue=11 |pages=4300–7 |year=2006 |pmid=16484588 |doi=10.1182/blood-2005-11-4433] [cite journal |author=Jenkins JM, Williams D, Deng Y, "et al" |title=Phase 1 clinical study of eltrombopag, an oral, nonpeptide thrombopoietin receptor agonist |journal=Blood |volume=109 |issue=11 |pages=4739–41 |year=2007 |pmid=17327409 |doi=10.1182/blood-2006-11-057968] ]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
Further reading
PBB_Further_reading
citations =
*cite journal | author=Kato T, Matsumoto A, Ogami K, "et al." |title=Native thrombopoietin: structure and function |journal=Stem Cells |volume=16 |issue= 5 |pages= 322–8 |year= 1999 |pmid= 9766811 |doi=
*cite journal | author=Kato T |title=Protein characteristics of thrombopoietin |journal=Stem Cells |volume=14 Suppl 1 |issue= |pages= 139–47 |year= 2000 |pmid= 11012214 |doi=
*cite journal | author=Geddis AE, Linden HM, Kaushansky K |title=Thrombopoietin: a pan-hematopoietic cytokine |journal=Cytokine Growth Factor Rev. |volume=13 |issue= 1 |pages= 61–73 |year= 2002 |pmid= 11750880| doi=10.1016/S1359-6101(01)00030-2
*cite journal | author=von dem Borne A, Folman C, van den Oudenrijn S, "et al." |title=The potential role of thrombopoietin in idiopathic thrombocytopenic purpura |journal=Blood Rev. |volume=16 |issue= 1 |pages= 57–9 |year= 2002 |pmid= 11913997 |doi= 10.1054/blre.2001.0184
*cite journal | author=Kaushansky K |title=Thrombopoietin: from theory to reality |journal=Int. J. Hematol. |volume=76 Suppl 1 |issue= |pages= 343–5 |year= 2003 |pmid= 12430879 |doi=
*cite journal | author=Kralovics R, Skoda RC |title=Molecular pathogenesis of Philadelphia chromosome negative myeloproliferative disorders |journal=Blood Rev. |volume=19 |issue= 1 |pages= 1–13 |year= 2005 |pmid= 15572213 |doi= 10.1016/j.blre.2004.02.002
*cite journal | author=Migliaccio AR, Rana RA, Vannucchi AM, Manzoli FA |title=Role of thrombopoietin in mast cell differentiation |journal=Ann. N. Y. Acad. Sci. |volume=1106 |issue= |pages= 152–74 |year= 2007 |pmid= 17468237 |doi= 10.1196/annals.1392.024
*cite journal | author=Foster DC, Sprecher CA, Grant FJ, "et al." |title=Human thrombopoietin: gene structure, cDNA sequence, expression, and chromosomal localization |journal=Proc. Natl. Acad. Sci. U.S.A. |volume=91 |issue= 26 |pages= 13023–7 |year= 1995 |pmid= 7809166 |doi=
*cite journal | author=Ritchie A, Vadhan-Raj S, Broxmeyer HE. |title=Thrombopoietin suppresses apoptosis and behaves as a survival factor for the human growth factor-dependent cell line, M07e. |journal=Stem Cells. |volume=14 |issue=3 |pages=330-6 |year=1996 |pmid=8724699
*cite journal | author=Chang MS, McNinch J, Basu R, "et al." |title=Cloning and characterization of the human megakaryocyte growth and development factor (MGDF) gene |journal=J. Biol. Chem. |volume=270 |issue= 2 |pages= 511–4 |year= 1995 |pmid= 7822271 |doi=
*cite journal | author=Gurney AL, Kuang WJ, Xie MH, "et al." |title=Genomic structure, chromosomal localization, and conserved alternative splice forms of thrombopoietin |journal=Blood |volume=85 |issue= 4 |pages= 981–8 |year= 1995 |pmid= 7849319 |doi=
*cite journal | author=Sohma Y, Akahori H, Seki N, "et al." |title=Molecular cloning and chromosomal localization of the human thrombopoietin gene |journal=FEBS Lett. |volume=353 |issue= 1 |pages= 57–61 |year= 1994 |pmid= 7926023| doi=10.1016/0014-5793(94)01008-0
*cite journal | author=Bartley TD, Bogenberger J, Hunt P, "et al." |title=Identification and cloning of a megakaryocyte growth and development factor that is a ligand for the cytokine receptor Mpl |journal=Cell |volume=77 |issue= 7 |pages= 1117–24 |year= 1994 |pmid= 8020099| doi=10.1016/0092-8674(94)90450-2
*cite journal | author=de Sauvage FJ, Hass PE, Spencer SD, "et al." |title=Stimulation of megakaryocytopoiesis and thrombopoiesis by the c-Mpl ligand |journal=Nature |volume=369 |issue= 6481 |pages= 533–8 |year= 1994 |pmid= 8202154 |doi= 10.1038/369533a0
*cite journal | author=Kaushansky K, Lok S, Holly RD, "et al." |title=Promotion of megakaryocyte progenitor expansion and differentiation by the c-Mpl ligand thrombopoietin |journal=Nature |volume=369 |issue= 6481 |pages= 568–71 |year= 1994 |pmid= 8202159 |doi= 10.1038/369568a0
*cite journal | author=Wendling F, Maraskovsky E, Debili N, "et al." |title=cMpl ligand is a humoral regulator of megakaryocytopoiesis |journal=Nature |volume=369 |issue= 6481 |pages= 571–4 |year= 1994 |pmid= 8202160 |doi= 10.1038/369571a0
*cite journal | author=Kato T, Ogami K, Shimada Y, "et al." |title=Purification and characterization of thrombopoietin |journal=J. Biochem. |volume=118 |issue= 1 |pages= 229–36 |year= 1996 |pmid= 8537317 |doi=
*cite journal | author=Hoffman RC, Andersen H, Walker K, "et al." |title=Peptide, disulfide, and glycosylation mapping of recombinant human thrombopoietin from ser1 to Arg246 |journal=Biochemistry |volume=35 |issue= 47 |pages= 14849–61 |year= 1997 |pmid= 8942648 |doi= 10.1021/bi961075b
*cite journal | author=Wiestner A, Schlemper RJ, van der Maas AP, Skoda RC |title=An activating splice donor mutation in the thrombopoietin gene causes hereditary thrombocythaemia |journal=Nat. Genet. |volume=18 |issue= 1 |pages= 49–52 |year= 1998 |pmid= 9425899 |doi= 10.1038/ng0198-49
*cite journal | author=Kondo T, Okabe M, Sanada M, "et al." |title=Familial essential thrombocythemia associated with one-base deletion in the 5'-untranslated region of the thrombopoietin gene |journal=Blood |volume=92 |issue= 4 |pages= 1091–6 |year= 1998 |pmid= 9694695 |doi=
External links
* [http://www.priory.com/med/thrombo.htm Longer summary on thrombopoietin]
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