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.