MPL
Overview
MPL encodes the thrombopoietin receptor (TPOR/CD110), a cytokine receptor that activates JAK-STAT signaling in hematopoietic progenitor cells. Activating mutations in MPL — most commonly W515L/K — are found in JAK2-negative myeloproliferative neoplasms (MPNs), particularly essential thrombocythemia (ET) and primary myelofibrosis (MF). MPL, JAK2, and CALR mutations are mutually exclusive, together accounting for the driver in the vast majority of MPN patients.
Alterations observed in the corpus
- Activating mutations in 7 MPN patients (all ET or MF) with unmutated JAK2; strictly mutually exclusive with CALR and JAK2 mutations in a large WES cohort of 197 MPN patients PMID:24325359
Cancer types (linked)
- Essential thrombocythemia (ET) — activating MPL mutations present in JAK2/CALR-negative cases PMID:24325359
- Primary myelofibrosis (MF) — activating MPL mutations present in JAK2/CALR-negative cases PMID:24325359
Co-occurrence and mutual exclusivity
- Mutually exclusive with JAK2 (V617F) and CALR (exon 9 indels); combined JAK2+MPL+CALR testing captures a driver in 146/151 (97%) of MPN patients PMID:24325359
Therapeutic relevance
- JAK1/2 inhibitors (ruxolitinib) used in MF and ET target the downstream JAK-STAT pathway shared by MPL, JAK2, and CALR-mutant disease.
Open questions
- The precise distribution of MPL mutation subtypes (W515L vs W515K vs others) was not detailed in the WES cohort PMID:24325359
Sources
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