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.
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.
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. The first 155 amino acids of the protein share homology with erythropoietin.
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.
Therapeutic use
Despite numerous trials, thrombopoietin has not been found to be useful therapeutically. Theoretical uses include the procurement of platelets for donation, and recovery of platelet counts after myelosuppressive chemotherapy. Romiplostim and Eltrombopag, compounds that are structurally different to thrombopoietin but stimulate the same pathway by binding to and activating the thrombopoietin receptor, are used instead.
A quadrivalent peptide analogue is being investigated, as well as several small-molecule agents,
Discovery
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.