THPO

THPO is the gene that encodes thrombopoietin, a cytokine that regulates the production of platelets. In humans, thrombopoietin is produced primarily by the liver, with additional contributions from the kidney and bone marrow stromal cells.

Function and mechanism

Thrombopoietin binds to the MPL receptor (also known as c-Mpl) on megakaryocyte progenitors and mature megakaryocytes, stimulating their proliferation, differentiation, and maturation. This signaling activates intracellular pathways such as JAK2-STAT, MAPK, and PI3K-AKT, promoting platelet production. The process links platelet mass to thrombopoietin availability through a feedback mechanism: platelets and megakaryocytes express MPL and clear circulating TPO; when platelet counts are low, circulating TPO rises to stimulate production.

Regulation and genetics

THPO expression is regulated by hepatic transcriptional networks and can be influenced by systemic conditions affecting the liver. Genetic defects affecting THPO or its receptor MPL can lead to thrombocytopenia. Congenital amegakaryocytic thrombocytopenia can arise from mutations in THPO or MPL, illustrating the essential role of this axis in platelet formation.

Clinical significance

Thrombopoietin and its receptor are targets of therapy for thrombocytopenia. While recombinant human thrombopoietin use faced challenges due to antibody formation, thrombopoietin receptor agonists (such as romiplostim and eltrombopag) are used to increase platelet counts in conditions like immune thrombocytopenia. Understanding THPO and MPL signaling is also relevant in broader contexts of liver disease and bone marrow function where platelet production is impacted.