Features and allele frequency of JAK2 Exon 12-mutated polycythemia vera in comparison with JAK2V617F-mutated disease

Background and Aim: JAK2 exon 12 mutation status and the clinical characteristics of patients with polycythemia vera (PV) in Asia remain to be defined. Method: We analyzed the clinical, molecular, and genetic features and outcomes of patients with PV harboring exon 12 mutation and compared them with the JAK2V617F-mutated patients in Taiwan. JAK2V617F with allele burden was measured by pyrosequencing and/or RT/qPCR. The allele frequency of exon 12 mutation was analyzed by next-generation sequencing in JAK2V617F-negative patients. Results: A total of 532 patients diagnosed with PV were enrolled. The JAK2V617F mutation was present in 94.9% and exon 12 mutations in 5.1%. At diagnosis, patients with exon 12 mutation had higher hemoglobin (p = 0.012), and hematocrit levels (p = 0.003), and lower platelet (p < 0.001), and leukocyte counts (p < 0.001) compared to patients with JAK2V617F mutations. Patients harboring the JAK2V617F mutation had a higher incidence of high allele burden (p < 0.001), disease risk (p = 0.014), and bleeding events (p = 0.013) compared to patients with PV with exon 12 mutations. These patients showed similar outcomes (overall survival, leukemia-free, myelofibrosis and thrombosis-free survival) to those with JAK2V617F mutations. An allele frequency ≥ 52.5% conferred an inferior overall survival compared to ≤ 52.5% in both exon 12-mutated (p = 0.029) and JAK2V617F patients with PV (p = 0.038). Conclusion: Taiwanese patients with PV showed differences in blood count, risk group, and bleeding events between exon 12 and JAK2V617F patients. Higher mutant allele burden had a negative impact on overall survival for both mutation types.