# MPN driver mutations (JAK2 V617F, CALR, MPL) and allele burden

Source: https://onco.cc/terms/mpn-driver-mutations/  
OnCo record `mpn-driver-mutations` (Term). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

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.

## Fields

- Kind: Term
- Last checked: 2026-09-17
- Also known as: 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

## Connected records

- targets: [JAK2](https://onco.cc/targets/jak2/)
- terms: [DIPSS, DIPSS-plus and MIPSS70 (myelofibrosis risk scores)](https://onco.cc/terms/dipss-mipss70/), [IPSET-thrombosis score (essential thrombocythaemia)](https://onco.cc/terms/ipset-thrombosis/), [Molecular response (MMR, MR4, treatment-free remission)](https://onco.cc/terms/molecular-response/), [Next-generation sequencing (NGS)](https://onco.cc/terms/ngs/), [Variant allele frequency (VAF)](https://onco.cc/terms/vaf/)
- drugs: [Hydroxyurea (hydroxycarbamide)](https://onco.cc/drugs/hydroxyurea/), [Interferon alfa-2a/2b](https://onco.cc/drugs/interferon-alfa/), [Ruxolitinib](https://onco.cc/drugs/ruxolitinib/)
- cancers: [Essential thrombocythaemia (ET)](https://onco.cc/cancers/essential-thrombocythaemia/), [Polycythaemia vera (PV)](https://onco.cc/cancers/polycythaemia-vera/), [Primary myelofibrosis](https://onco.cc/cancers/primary-myelofibrosis/)

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