Last updated
Protein THPO PDB 1v7m.png
Available structures
PDB Ortholog search: PDBe RCSB
Aliases THPO , MGDF, MKCSF, ML, MPLLG, THCYT1, TPO, thrombopoietin
External IDs OMIM: 600044 MGI: 101875 HomoloGene: 398 GeneCards: THPO
RefSeq (mRNA)


RefSeq (protein)


Location (UCSC) Chr 3: 184.37 – 184.38 Mb Chr 16: 20.54 – 20.55 Mb
PubMed search [3] [4]
View/Edit Human View/Edit Mouse

Thrombopoietin (THPO) also known as megakaryocyte growth and development factor (MGDF) is a protein that in humans is encoded by the THPO gene.

Thrombopoietin is a glycoprotein hormone produced by the liver and kidney which regulates the production of platelets. It stimulates the production and differentiation of megakaryocytes, the bone marrow cells that bud off large numbers of platelets. [5]

Megakaryocytopoiesis is the cellular development process that leads to platelet production. The protein encoded by this gene is a humoral growth factor 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. [6]


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. The first 155 amino acids of the protein share homology with erythropoietin. [7]

Function and regulation

Thrombopoietin is produced in the liver by both parenchymal cells and sinusoidal endothelial cells, as well as in the kidney by proximal convoluted tubule cells. Small amounts are also made by striated muscle and bone marrow stromal cells. [5] In the liver, its production is augmented by interleukin 6 (IL-6). [5] However, the liver and the kidney are the primary sites of thrombopoietin production.

Thrombopoietin regulates the differentiation of megakaryocytes and platelets, but studies on the removal of the thrombopoietin receptor show that its effects on hematopoiesis are more versatile. [5]

Its negative feedback is different from that of most hormones in endocrinology: The effector regulates the hormone directly. Thrombopoietin is bound to the surface of platelets and megakaryocytes by the mpl receptor (CD 110). Inside the platelets it gets destroyed, while inside the megakaryocytes it gives the signal of their maturation and consecutively more platelet production. The bounding of the hormone at these cells thereby reduces further megakaryocyte exposure to the hormone. [5] Therefore, the rising and dropping platelet and megakaryocyte concentrations regulate the thrombopoietin levels. Low platelets and megakaryocytes lead a higher degree of thrombopoietin exposure to the undifferentiated bone marrow cells, leading to differentiation into megakaryocytes and further maturation of these cells. On the other hand, high platelet and megakaryocyte concentrations lead to more thrombopoetin destruction and thus less availability of thrombopoietin to bone marrow.

TPO, like EPO, plays a role in brain development. It promotes apoptosis of newly generated neurons, an effect counteracted by EPO and neurotrophins. [8]

Therapeutic use

Despite numerous trials, thrombopoietin has not been found to be useful therapeutically. Theoretical uses include the procurement of platelets for donation, [9] and recovery of platelet counts after myelosuppressive chemotherapy. [5]

Trials of a modified recombinant form, megakaryocyte growth and differentiation factor (MGDF), were stopped when healthy volunteers developed autoantibodies to endogenous thrombopoietin and then developed thrombocytopenia. [10] Romiplostim and Eltrombopag, structurally different compounds that stimulate the same pathway, are used instead. [11]

A quadrivalent peptide analogue is being investigated, as well as several small-molecule agents, [5] and several non-peptide ligands of c-Mpl, which act as thrombopoietin analogues. [12] [13]


Thrombopoietin was cloned by five independent teams 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. [5]

See also

Related Research Articles

<span class="mw-page-title-main">Platelet</span> Component of blood aiding in coagulation

Platelets or thrombocytes are a component of blood whose function is to react to bleeding from blood vessel injury by clumping, thereby initiating a blood clot. Platelets have no cell nucleus; they are fragments of cytoplasm derived from the megakaryocytes of the bone marrow or lung, which then enter the circulation. Platelets are found only in mammals, whereas in other vertebrates, thrombocytes circulate as intact mononuclear cells.

<span class="mw-page-title-main">Immune thrombocytopenic purpura</span> Medical condition with rash and bleeding risk

Immune thrombocytopenic purpura (ITP), also known as idiopathic thrombocytopenic purpura or immune thrombocytopenia, is a type of thrombocytopenic purpura characterized by a low platelet count in the absence of other causes, and accompanied by a red-purple rash called purpura. It leads to an increased risk of bleeding. ITP manifests in two distinct clinical syndromes: an acute form observed in children, and chronic conditions observed in adults. The acute form often follows an infection and typically resolves within two months, while chronic immune thrombocytopenia persists for longer than six months and its specific cause is unknown.

<span class="mw-page-title-main">Megakaryocyte</span> Type of bone marrow cell

A megakaryocyte is a large bone marrow cell with a lobated nucleus that produces blood platelets (thrombocytes), which are necessary for normal clotting. In humans, megakaryocytes usually account for 1 out of 10,000 bone marrow cells, but can increase in number nearly 10-fold during the course of certain diseases. Owing to variations in combining forms and spelling, synonyms include megalokaryocyte and megacaryocyte.

Primary myelofibrosis (PMF) is a rare bone marrow blood cancer. It is classified by the World Health Organization (WHO) as a type of myeloproliferative neoplasm, a group of cancers in which there is activation and growth of mutated cells in the bone marrow. This is most often associated with a somatic mutation in the JAK2, CALR, or MPL genes. In PMF, the bony aspects of bone marrow are remodeled in a process called osteosclerosis; in addition, fibroblast secrete collagen and reticulin proteins that are collectively referred to as (fibrosis). These two pathological processes compomise the normal function of bone marrow resulting in decreased production of blood cells such as erythrocytes granulocytes and megakaryocytes, the latter cells responsible for the production of platelets.

<span class="mw-page-title-main">Myeloproliferative neoplasm</span> Medical condition

Myeloproliferative neoplasms (MPNs) are a group of rare blood cancers in which excess red blood cells, white blood cells or platelets are produced in the bone marrow. Myelo refers to the bone marrow, proliferative describes the rapid growth of blood cells and neoplasm describes that growth as abnormal and uncontrolled.

<span class="mw-page-title-main">CD34</span> Cluster of differentiation protocol that identifies cell surface antigens.

CD34 is a transmembrane phosphoglycoprotein protein encoded by the CD34 gene in humans, mice, rats and other species.

<span class="mw-page-title-main">GATA1</span> Protein-coding gene in humans

GATA-binding factor 1 or GATA-1 is the founding member of the GATA family of transcription factors. This protein is widely expressed throughout vertebrate species. In humans and mice, it is encoded by the GATA1 and Gata1 genes, respectively. These genes are located on the X chromosome in both species.

<span class="mw-page-title-main">Platelet factor 4</span> Protein involved in blood clotting, wound healing and inflammation

Platelet factor 4 (PF4) is a small cytokine belonging to the CXC chemokine family that is also known as chemokine ligand 4 (CXCL4). This chemokine is released from alpha-granules of activated platelets during platelet aggregation, and promotes blood coagulation by moderating the effects of heparin-like molecules. Due to these roles, it is predicted to play a role in wound repair and inflammation. It is usually found in a complex with proteoglycan.

<span class="mw-page-title-main">Interleukin 11</span> Protein-coding gene in the species Homo sapiens

Interleukin 11 is a protein that in humans is encoded by the IL11 gene.

<span class="mw-page-title-main">Stem cell factor</span> Mammalian protein found in Homo sapiens

Stem cell factor is a cytokine that binds to the c-KIT receptor (CD117). SCF can exist both as a transmembrane protein and a soluble protein. This cytokine plays an important role in hematopoiesis, spermatogenesis, and melanogenesis.

<span class="mw-page-title-main">ETV6</span> Protein-coding gene in the species Homo sapiens

ETV6 protein is a transcription factor that in humans is encoded by the ETV6 gene. The ETV6 protein regulates the development and growth of diverse cell types, particularly those of hematological tissues. However, its gene, ETV6 frequently suffers various mutations that lead to an array of potentially lethal cancers, i.e., ETV6 is a clinically significant proto-oncogene in that it can fuse with other genes to drive the development and/or progression of certain cancers. However, ETV6 is also an anti-oncogene or tumor suppressor gene in that mutations in it that encode for a truncated and therefore inactive protein are also associated with certain types of cancers.

<span class="mw-page-title-main">Eltrombopag</span> Chemical compound

Eltrombopag, sold under the brand name Promacta among others, is a medication used to treat thrombocytopenia and severe aplastic anemia. Eltrombopag is sold under the brand name Revolade outside the US and is marketed by Novartis. It is a thrombopoietin receptor agonist. It is taken by mouth.

The Harrington–Hollingsworth experiment was an experiment that established the autoimmune nature of the blood disorder immune thrombocytopenic purpura. It was performed in 1950 by the academic staff of Barnes-Jewish Hospital in St. Louis, Missouri.

<span class="mw-page-title-main">Thrombopoietin receptor</span> Protein-coding gene in the species Homo sapiens

The thrombopoietin receptor also known as the myeloproliferative leukemia protein or CD110 is a protein that in humans is encoded by the MPL oncogene.

<span class="mw-page-title-main">SH2B3</span> Protein-coding gene in the species Homo sapiens

SH2B adapter protein 3 (SH2B3), also known as lymphocyte adapter protein (LNK), is a protein that in humans is encoded by the SH2B3 gene on chromosome 12.

<span class="mw-page-title-main">Congenital amegakaryocytic thrombocytopenia</span> Medical condition

Congenital amegakaryocytic thrombocytopenia (CAMT) is a rare inherited disorder caused by mutations in the c-mpl gene. It is often diagnosed in the neonatal period due to petechia. It begins with congenital thrombocytopenia and can progress to aplastic anemia. It is associated with leukemia.

<span class="mw-page-title-main">Thrombopoiesis</span>

Thrombopoiesis is the formation of thrombocytes in the bone marrow. Thrombopoietin is the main regulator of thrombopoiesis. Thrombopoietin affects most aspects of the production of platelets. This includes self-renewal and expansion of hematopoietic stem cells, stimulating the increase of megakaryocyte progenitor cells, and supporting these cells so they mature to become platelet-producing cells. The process of Thrombopoiesis is caused by the breakdown of proplatelets. During the process almost all of the membranes, organelles, granules, and soluble macromolecules in the cytoplasm are being consumed. Apoptosis also plays a role in the final stages of thrombopoiesis by letting proplatelet processes to occur from the cytoskeleton of actin.

Kenneth Kaushansky, M.D., Master of the American College of Physicians (MACP) is an American medical doctor, hematologist, former editor of the medical journal Blood, and has served as the dean of the Stony Brook University School of Medicine since July 2010. Prior to moving to Stony Brook, he was the Helen M. Ranney Professor, and chair of the department of medicine at University of California, San Diego School of Medicine.

<span class="mw-page-title-main">Avatrombopag</span> Chemical compound

Avatrombopag, sold under the brand name Doptelet, is a medication that used for certain conditions that lead to thrombocytopenia such as thrombocytopenia associated with chronic liver disease in adults who are to undergo a planned medical or dental procedure. It was approved for medical use in the United States in May 2018, the European Union in June 2019, and Australia in January 2023.

<span class="mw-page-title-main">William Vainchenker</span>

William Vainchenker, born on 16 December 1947, is a French medical doctor and researcher. He is considered a specialist in hematopoiesis.


  1. 1 2 3 GRCh38: Ensembl release 89: ENSG00000090534 - Ensembl, May 2017
  2. 1 2 3 GRCm38: Ensembl release 89: ENSMUSG00000022847 - Ensembl, May 2017
  3. "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  5. 1 2 3 4 5 6 7 8 Kaushansky K (May 2006). "Lineage-specific hematopoietic growth factors". The New England Journal of Medicine. 354 (19): 2034–45. doi:10.1056/NEJMra052706. PMID   16687716.
  6. "Entrez Gene: THPO thrombopoietin (myeloproliferative leukemia virus oncogene ligand, megakaryocyte growth and development factor)".
  7. Online Mendelian Inheritance in Man (OMIM): 600044
  8. Ehrenreich H, Hasselblatt M, Knerlich F, von Ahsen N, Jacob S, Sperling S, et al. (January 2005). "A hematopoietic growth factor, thrombopoietin, has a proapoptotic role in the brain". Proceedings of the National Academy of Sciences of the United States of America. 102 (3): 862–7. Bibcode:2005PNAS..102..862E. doi: 10.1073/pnas.0406008102 . PMC   545528 . PMID   15642952.
  9. Kuter DJ, Goodnough LT, Romo J, DiPersio J, Peterson R, Tomita D, et al. (September 2001). "Thrombopoietin therapy increases platelet yields in healthy platelet donors". Blood. 98 (5): 1339–45. doi: 10.1182/blood.V98.5.1339 . PMID   11520780. S2CID   12119556.
  10. Li J, Yang C, Xia Y, Bertino A, Glaspy J, Roberts M, Kuter DJ (December 2001). "Thrombocytopenia caused by the development of antibodies to thrombopoietin". Blood. 98 (12): 3241–8. doi: 10.1182/blood.V98.12.3241 . PMID   11719360.
  11. Imbach P, Crowther M (August 2011). "Thrombopoietin-receptor agonists for primary immune thrombocytopenia". The New England Journal of Medicine. 365 (8): 734–41. doi:10.1056/NEJMct1014202. PMID   21864167.
  12. Nakamura T, Miyakawa Y, Miyamura A, Yamane A, Suzuki H, Ito M, et al. (June 2006). "A novel nonpeptidyl human c-Mpl activator stimulates human megakaryopoiesis and thrombopoiesis". Blood. 107 (11): 4300–7. doi: 10.1182/blood-2005-11-4433 . PMID   16484588.
  13. Jenkins JM, Williams D, Deng Y, Uhl J, Kitchen V, Collins D, Erickson-Miller CL (June 2007). "Phase 1 clinical study of eltrombopag, an oral, nonpeptide thrombopoietin receptor agonist". Blood. 109 (11): 4739–41. doi: 10.1182/blood-2006-11-057968 . PMID   17327409.

Further reading