MPL (myeloproliferative leukemia virus oncogene) is the gene on chromosome 1p34 that encodes the thrombopoietin receptor (TPO-R/TPOR, also called CD110 or c-Mpl), a type I transmembrane cytokine receptor essential for hematopoietic stem cell (HSC) maintenance and megakaryopoiesis.
The MPL gene encodes the thrombopoietin receptor, also called c-Mpl.
This receptor helps regulate the production of platelets and the development of blood-forming stem cells in the bone marrow.
Ii is one of the three driver mutations of BCR::ABL1-negative myeloproliferative neoplasms (MPNs) — alongside JAK2 and CALR.
MPL binds thrombopoietin, triggering JAK2 activation and downstream STAT, RAS–MAPK, and PI3K signaling.
It is the principal cytokine receptor regulating HSC self-renewal, megakaryocyte development, and platelet production.
Notably, MPL is the convergence point for all three MPN drivers: JAK2 V617F activates MPL directly, and mutant CALR binds and dimerizes MPL, so enhanced MPL–JAK–STAT signaling unifies MPN pathogenesis.
MPL mutations in MPN-Mutations cluster in exon 10 around codon W515 , most commonly W515L and W515K, causing ligand-independent (constitutive) receptor dimerization and activation.
S505N (transmembrane domain) is seen both as a somatic mutation and as the classic cause of familial/hereditary essential thrombocythemia.
Phenotype: MPL-mutant disease presents as essential thrombocythemia (ET) or primary myelofibrosis (PMF), not polycythemia vera — because mutant MPL (like mutant CALR) selectively drives the megakaryocytic lineage.
Prevalence: found in roughly 4% of ET and up to ~10% of PMF (JAK2-negative cases), and MPL mutations are typically mutually exclusive with JAK2/CALR.
MPL is part of the standard molecular diagnostic workup (multigene panel for JAK2/CALR/MPL) for suspected MPN, and satisfies a major diagnostic criterion for ET and PMF
MPL W515L/K carries an intermediate prognosis and a higher thrombosis risk compared with CALR type 1 mutations in myelofibrosis.
Clinically:
Inherited MPL mutations can cause congenital amegakaryocytic thrombocytopenia, leading to very low platelet counts.
Acquired MPL mutations, especially W515L and W515K are associated with myeloproliferative neoplasms such as: Primary myelofibrosis Essential thrombocythemia
MPL mutations are usually tested alongside JAK2 and CALR mutations when evaluating unexplained high platelet counts or suspected myeloproliferative neoplasms.
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