Janus Kinase 2 V617F Allele Burden and its Correlation with Thrombotic Risk in Myeloproliferative Neoplasms: A Prospective Observational Study

Abstract

Background: Janus Kinase 2 (JAK2) V617F mutation is a key molecular marker in Philadelphia chromosome-negative myeloproliferative neoplasms (MPNs), but the clinical relevance of allele burden in thrombotic risk stratification remains under evaluation. Methods: This prospective observational study included 120 patients with MPNs at a tertiary hospital from June 2025 to May 2026. JAK2 V617F allele burden was assessed and categorized as negative, low (<25%), intermediate (25–50%), and high (>50%). Associations with clinical, hematological, and thrombotic outcomes were analyzed. Results: JAK2 V617F mutation was detected in 94 patients (78.3%). Median allele burden was highest in polycythemia vera (59.0%), followed by primary myelofibrosis (40.1%) and essential thrombocythemia (18.1%) (P < 0.001). High allele burden was present in 42 patients (35.0%) and was associated with leukocytosis, splenomegaly, high thrombotic risk category, prior thrombosis, venous thrombosis, and overall thrombotic events. Overall thrombotic events increased across allele burden categories and were highest in the high allele burden group (59.5%). Allele burden correlated positively with hemoglobin, hematocrit, leukocyte count, lactate dehydrogenase, and thrombotic risk score and inversely with platelet count. On multivariable analysis, allele burden remained independently associated with high thrombotic risk category (adjusted odds ratio [OR] 1.38/10% increase) and overall thrombotic events (adjusted OR 1.34/10% increase). Conclusion: Higher JAK2 V617F allele burden was associated with proliferative disease features and increased thrombotic risk, particularly venous and overall thrombotic events, supporting its role as an adjunctive biomarker in MPN risk stratification.