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

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.