MPN-364: The Clinical Significance of JAK2V617F Mutational Status on Phenotypic Features in Philadelphia-Negative Chronic Myeloproliferative Neoplasms

Abstract

Context: The JAK2V617F mutation is present in the majority of patients with polycythemia vera (PV), essential thrombocythemia (ET), and primary myelofibrosis (PMF). The impact of this mutation on disease phenotype in the aforementioned diseases is still a matter of discussion. This study aims to determine differences in clinical presentation and disease outcome among PV, ET, and PMF patients with and without the JAK2V617F mutation. Objective: A total of 410 consecutive Philadelphia-negative MPN patients, 170 with ET, 135 with PV, and 105 with PMF under follow-up between 1995 and 2020 were included in this study. Methods: Two hundred twenty-eight patients (118 ET, 84 PMF, 26 PV) were genotyped for the JAK2V617F mutation with the JAK2 MutaScreen assay (Ipsogen, Luminy Biotech, Marseille, France). In 182 patients (109 PV, 52 ET, 21 PMF), JAK2V617F mutation was detected by LightCycler techniques, which is genotype assessment based on melting curve analysis. Results: In our study, the JAK2V617 mutation-positive PV group consisted of a significantly lower number of male patients (p=0.008). JAK2V617F mutation-positive PV patients had significantly higher leukocyte and platelet counts and lower Hgb levels (p=0.001; p=0.001 and p=0.018, respectively). Rates of total thrombosis and arterial thrombosis were significantly higher in JAK2V617F mutation-positive PV compared to JAK2V617F mutation-negative PV (42.7%, 20%; respectively; p=0.035 and 26.4%, 8%; respectively; p=0.042). In our study, JAK2V617F mutation-positive ET patients had significantly higher Hgb and Htc levels and lower platelet counts at initial diagnosis (p=0.001; p=0.001 and p=0.001, respectively). The JAK2V617 mutation-negative PMF group consisted of a significantly higher number of female patients (p=0.001). In PMF patients, the presence of JAK2V617F mutation was significantly associated with increased spleen size (p=0.042) and higher leukocyte count (p=0.019). There was a trend toward higher incidence of venous thrombosis in JAK2V617F mutation-positive PMF compared to JAK2V617F mutation-negative PMF (10%; 0; respectively; p=0.051) patients. Conclusion: We conclude that JAK2V617F-mutated ET patients express a PV-like phenotype, JAK2V617F mutation in PMF patients is associated with a more pronounced myeloproliferative phenotype and higher incidence of venous thrombosis, and JAK2V617F-mutated PV patients express a higher rate of total thrombosis and arterial thrombosis.