{"entity":{"id":"mpn-driver-mutations","kind":"term","name":"MPN driver mutations (JAK2 V617F, CALR, MPL) and allele burden","aka":["JAK2 V617F","JAK2 mutation","JAK2-positive","JAK2-negative","JAK2 exon 12","CALR","CALR mutation","CALR type 1","CALR type 2","MPL W515","MPL mutation","triple-negative MPN","triple negative myeloproliferative neoplasm","JAK2 allele burden","JAK2 variant allele fraction","MPN driver mutation"],"tldr":"Almost every polycythaemia vera and most essential thrombocythaemia and myelofibrosis carry one of three mutations (JAK2 V617F, CALR or MPL) that jam the growth signal on; finding one confirms the diagnosis is a true blood cancer rather than a reaction to something else, and the mutation type and how much of the blood carries it shape the risk of clots and progression.","summary":"What is measured: the clonal driver of a myeloproliferative neoplasm and its allele burden. How: peripheral blood PCR (allele-specific quantitative or digital PCR for JAK2 V617F with the percentage of mutant alleles, sequencing for JAK2 exon 12, CALR exon 9 insertions and deletions typed 1 or 2, and MPL exon 10 W515 variants) or a myeloid sequencing panel that also reports high-molecular-risk mutations (ASXL1, SRSF2, EZH2, IDH1, IDH2, U2AF1) and TP53. Frequencies: polycythaemia vera JAK2 V617F about 95 percent and exon 12 about 3 percent; essential thrombocythaemia JAK2 about 60 percent, CALR 25, MPL 3, triple-negative 10; primary myelofibrosis JAK2 60, CALR 25, MPL 7, triple-negative 10 (the worst group). A driver is a WHO 2022 major criterion. What a result changes: JAK2 V617F in essential thrombocythaemia raises thrombosis risk in the IPSET score and so the threshold for aspirin and cytoreduction; type 1 CALR in myelofibrosis predicts longer survival and triple-negative shorter (MIPSS70); an allele burden above 50 percent in polycythaemia vera tracks with fibrotic progression; the burden falls with ropeginterferon alfa-2b (a molecular response) but little with hydroxyurea or ruxolitinib, and it serves as a residual-disease marker after transplant. JAK inhibitors work whichever driver is present. Where it matters: polycythaemia vera, essential thrombocythaemia and primary myelofibrosis.","asOf":"2026-09-17","links":[],"tags":[],"related":["jak2","ngs","vaf","ruxolitinib","interferon-alfa","hydroxyurea","ipset-thrombosis","dipss-mipss70","molecular-response"],"cancers":["polycythaemia-vera","essential-thrombocythaemia","primary-myelofibrosis"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Biomarkers"},"route":"/terms/mpn-driver-mutations/","neighbours":{"target":[{"id":"jak2","kind":"target","name":"JAK2","route":"/targets/jak2/"}],"term":[{"id":"dipss-mipss70","kind":"term","name":"DIPSS, DIPSS-plus and MIPSS70 (myelofibrosis risk scores)","route":"/terms/dipss-mipss70/"},{"id":"ipset-thrombosis","kind":"term","name":"IPSET-thrombosis score (essential thrombocythaemia)","route":"/terms/ipset-thrombosis/"},{"id":"molecular-response","kind":"term","name":"Molecular response (MMR, MR4, treatment-free remission)","route":"/terms/molecular-response/"},{"id":"ngs","kind":"term","name":"Next-generation sequencing (NGS)","route":"/terms/ngs/"},{"id":"vaf","kind":"term","name":"Variant allele frequency (VAF)","route":"/terms/vaf/"}],"drug":[{"id":"hydroxyurea","kind":"drug","name":"Hydroxyurea (hydroxycarbamide)","route":"/drugs/hydroxyurea/"},{"id":"interferon-alfa","kind":"drug","name":"Interferon alfa-2a/2b","route":"/drugs/interferon-alfa/"},{"id":"ruxolitinib","kind":"drug","name":"Ruxolitinib","route":"/drugs/ruxolitinib/"}],"cancer":[{"id":"essential-thrombocythaemia","kind":"cancer","name":"Essential thrombocythaemia (ET)","route":"/cancers/essential-thrombocythaemia/"},{"id":"polycythaemia-vera","kind":"cancer","name":"Polycythaemia vera (PV)","route":"/cancers/polycythaemia-vera/"},{"id":"primary-myelofibrosis","kind":"cancer","name":"Primary myelofibrosis","route":"/cancers/primary-myelofibrosis/"}]}}