Results for thrombopoietin
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Oncology Encyclopedia:

Thrombopoietin

Key Terms: Investigational drug.

Definition

Thrombopoietin is an investigational or experimental drug that may increase the number of platelets in the bloodstream.

Purpose

Thrombopoietin is an experimental drug that may be used to treat thrombocytopenia (a reduced number of platelets in the blood).

Description

Thrombocytopenia, or a low number of platelets in the blood, can be a life-threatening condition. Platelets are necessary for the normal process of blood clotting. When someone experiences thrombocytopenia, a cut or bruise might not heal quickly, or at all, without medical intervention. Therefore, patients with a low platelet cell count must take special precautions, and suffer significant risk.

Thrombocytopenia is a common side effect from many common chemotherapy agents. These agents temporarily decrease the production of platelets, as well as white blood cells that fight infection and red blood cells that carry oxygen. Carboplatin is an example of an agent that has a tendency to lower platelet counts. Like other cells of the blood (white blood cells and red blood cells), the number of platelets will generally increase and return to normal over days and weeks following the administration of chemotherapy.

By reducing the severity of platelet-related side effects, thrombopoietin could allow the antitumor medication to be used at higher doses and/or for longer periods of time. Thrombopoietin may also be used in other situations in which patients have low platelet cell counts.

Thrombopoietin is derived from the gene of the same name. A laboratory-synthesized version of the human gene product encourages the development of platelet cells from precursor cells in the blood.

Thrombopoietin is an investigational, or an experimental, drug in the U.S.. This means that the FDA has not approved this drug for general use as of mid-2001. Generally, investigational drugs are made available through participation in clinical trials.

Recommended Dosage, Precautions, Side Effects, and Interactions

As noted above, investigational drugs generally are prescribed as part of a clinical trial. Clinical trials seek to determine how effective a drug is at treating the targeted condition, the effective dose of the drug, any precautions patients should take before the drug is administered, any side effects the drug may have, and any interactions the investigational drug may have with other drugs. Since thrombopoietin is investigational, it is premature to discuss dosage, precautions, side effects, and interactions.

—Michael Zuck, Ph.D.

 
 
Veterinary Dictionary: thrombopoietin

An α2-globulin, a hormone involved in the differentiation and maturation of platelets but thought to be responsible for regulating the supply of platelets.

 
Wikipedia: thrombopoietin
thrombopoietin (myeloproliferative leukemia virus oncogene ligand, megakaryocyte growth and development factor)
Identifiers
Symbol THPO
Alt. Symbols MGDF
Entrez 7066
HUGO 11795
OMIM 600044
RefSeq NM_199228
UniProt P40225
Other data
Locus Chr. 3 q27

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 platelets[1].

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[2].

Function and regulation

It is produced by the liver and kidney, as well as striated muscle and stromal cells in the bone marrow[1]. In the liver, its production is augmented by interleukin 6 (IL-6)[1].

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[1].

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[1].

Therapeutic use

Despite numerous trials, thrombopoeitin is not used therapeutically. Theoretical uses include the procurement of platelets for donation[3], recovery of platelet counts after myelosuppressive chemotherapy[1].

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[1].

A non-peptide ligand of c-Mpl, which acts as a thrombopoietin analogue, is under investigation[4]

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

  1. ^ a b c d e f g Kaushansky K. Lineage-specific hematopoietic growth factors. N Engl J Med 2006;354:2034-45. PMID 16687716.
  2. ^ Mendelian Inheritance in Man (OMIM) 600044
  3. ^ Kuter 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.
  4. ^ Nakamura 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.

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Copyrights:

Oncology Encyclopedia. Gale Encyclopedia of Cancer. Copyright © 2006 by The Gale Group, Inc. All rights reserved.  Read more
Veterinary Dictionary. Saunders Comprehensive Veterinary Dictionary 3rd Edition. Copyright © 2007 by D.C. Blood, V.P. Studdert and C.C. Gay, Elsevier. All rights reserved.  Read more
Wikipedia. This article is licensed under the GNU Free Documentation License. It uses material from the Wikipedia article "Thrombopoietin" Read more

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