Correlation of JAK2 V617F mutant allele quantitation with clinical presentation and type of chronic myeloproliferative neoplasm

Activating JAK2 V617F mutation is present in many patients with chronic myeloproliferative neoplasms. We evaluated, retrospectively, clinical and laboratory data from 70 patients with BCR-ABL1 negative, JAK2 positive, chronic myeloproliferative disease. Quantity of the JAK2 mutant allele was tested for correlation with the clinical presentation, type of chronic myeloproliferative disease, hemoglobin level, white blood cell and platelet counts, spleen size, and/or cardiovascular complications. RealTime-PCR was used for amplification of DNA from marrow or peripheral blood. Polycythemia vera was more frequently diagnosed among patients with ≥50% mutational load than among those with <50% mutational load (71% vs 25%; p = 0.003). Patients with ≥50% mutational load had higher mean white blood cell count (18.6 billion/L vs 11.3 billion/L; p = 0.043). Essential thrombocythemia patients were more likely to have <50% mutational load (48% vs 7%; p = 0.005). Splenomegaly was more frequent in patients with ≥50% mutational load independent of the diagnosis (89% vs 48%; p = 0.03). Cardiovascular complications were reported in 50% of patients with ≥50% mutational load vs 21% of patients with <50% mutational load. JAK2 quantitation was highest in polycythemia vera followed by chronic myeloproliferative disease, unclassifiable, and essential thrombocythemia patients. JAK2 quantitation appears important in clinical evaluation. Mutational load appears to be helpful in stratification of patients into subgroups with different frequency of complications. Quantitation of JAK2 mutational load may be useful in evaluating response to therapy.