cMpl

c-Mpl, also known as CD110 and the MPL receptor, is the cellular receptor for thrombopoietin (TPO). It is encoded by the MPL gene in humans and is expressed on hematopoietic stem cells, megakaryocyte progenitors, and, to varying degrees, platelets. The receptor is the cellular homolog of a viral oncogene (v-Mpl); together with its ligand, TPO, c-Mpl plays a central role in the regulation of platelet production and the maintenance of the megakaryocyte lineage.

Structurally, c-Mpl is a type I cytokine receptor. Binding of TPO induces receptor dimerization and activation of associated intracellular kinases, primarily JAK2. This triggers downstream signaling cascades, including the JAK-STAT, MAPK, and PI3K-Akt pathways, promoting proliferation, differentiation, and survival of megakaryocyte progenitors and mature megakaryocytes. The receptor's activity is tightly controlled to maintain platelet homeostasis; disruption can alter platelet counts.

Functionally, c-Mpl signaling supports thrombopoiesis and supports hematopoietic stem cell maintenance. In experimental models, loss of MPL results in reduced platelet production and impaired megakaryopoiesis, while overactive signaling can contribute to abnormal platelet or cell proliferation.

Clinical significance centers on MPL mutations and misregulation in myeloproliferative neoplasms (MPNs). Mutations in MPL, such as MPLW515L/K, can drive constitutive signaling and contribute to disease phenotypes. MPL signaling is also a therapeutic target; thrombopoietin receptor agonists that activate c-Mpl, such as romiplostim and eltrombog, are used to treat certain thrombocytopenias. The MPL pathway interacts with JAK2 signaling, a common node in several hematologic disorders.