JAK2MPLnegative

JAK2/MPL negative refers to patients with myeloproliferative neoplasms (MPNs) who lack the most common driver mutations in the JAK2 and MPL genes. The JAK2 V617F mutation is present in about 95 % of polycythemia vera, 50–60 % of essential thrombocythemia and 40–50 % of primary myelofibrosis. The MPL W515L or W515K mutations account for roughly 3–5 % of cases. Patients who do not harbor either of these mutations are classified as JAK2/MPL negative, and the diagnosis of MPN is then supported by clinical features, hematologic findings, and additional molecular testing such as for CALR (calreticulin) exon 9 mutations.

CALR mutations are found in approximately 20–30 % of essential thrombocythemia and 20‑25 % of primary myelofibrosis, rendering these patients negative for JAK2 and MPL. In the remaining 20 % of cases with no identifiable driver mutation – “triple‑negative” MPN – other rare or novel mutations have been described, including in genes such as LNK, ASXL1 and TET2, but no single mutation has yet replaced JAK2 or MPL as a diagnostic criterion.

The JAK2/MPL negative status influences prognosis and therapeutic strategies. While JAK inhibitor therapy (e.g., ruxolitinib) remains effective in most patients, drug response may differ by mutation status, with CALR‑positive patients often showing a more favorable platelet count response. Clinical guidelines recommend routine screening for JAK2 V617F and exon 12, MPL W515 mutations, followed by CALR testing when initial results are negative. Ongoing research aims to identify new driver mutations that could refine risk stratification and guide targeted therapies for this subgroup of MPN patients.