The impact of JAK2V617F mutation on Philadelphia-negative myeloproliferative neoplasms.

Background/aim JAK2V617F mutation is expressed in almost all polycthemia vera (PV), 55% of essential thrombocythemia (ET) and 65% of primary myelofibrosis (PMF) patients.Studies investigating phenotypic effects of JAK2V617F mutation on Philadelphia?negativemyeloproliferative neoplasms (Ph-negative MPNs) have reported controversial results. This study aims to determine the impact of JAK2V617F mutation on clinical phenotype and outcome in Ph-negative MPNs. Materials and methods Clinical correlates and long-term prognostic relevance of the JAK2V617F mutation were analyzed in 410Ph-negative MPNs-170 ET, 135 PV, 105 PMF- from two institutions and followed for a mean of 76.7 months (SD 62.1) (mean 87 months (SD 67.8), 70.4 months (SD 56.4), 68 months (SD 57.4), respectively for ET, PV and PMF). 228 patients were genotyped for JAK2V617F mutation using the JAK2 Ipsogen MutaScreen assay, which involves allele-specific polymerase chain reaction(PCR)and 182 patients were genotyped using Melting Curve analysis. Results In PV patients,JAK2V617F mutation was associated with higher rate in females, lower hemoglobin (Hgb) levels, higher leukocyte and platelet counts and higher prevalence of thrombosis(p=0.008; p=0.018; p=0.001; p=0.001 and p=0.035, respectively).In ET patients, JAK2V617F mutation was associated with higher Hgb and hematocrit (Hct) levels and lower platelet count(p=0.001; p=0.001 and p=0.001, respectively). JAK2V617F-negative ET patients showed a trend towards higher rate of leukemic transformation (p=0.061).JAK2V617F mutation positive PMF patients had higher leukocyte count, greater spleen size and showed a trend towards higher Hgb level(p=0.019; p=0.042 and p=0.056, respectively).Among PMF patients with JAK2V617F mutation, the rate of female patients was lower (p=0.001). Overall survival (OS) in Dynamic International Prognostic Scoring System (DIPSS)-plus high risk PMF patients was shorter compared to the other risk groups (p=0.001). Leukemia-free survival (LFS) was shorter in DIPSS-plus high risk PMF patients than the other risk groups (p=0.005). In the entire cohort of Ph-negative MPN patients, JAK2V617F mutation was associated with higher leukocyte count, higher Hgb and Hct levels and lower platelet count, higher frequency of phlebotomies, a trend towards older age, a trend towards greater spleen size, a trend towards a higher prevalence of risk factors for cardiovascular diseases and thrombosis (p=0.001; p=0.005; p=0.001; p=0.003, p=0.004; p=0.052; p=0.056; p=0.052 and p=0.059, respectively) Conclusion: In our study population, it was demonstrated that the presence of JAK2V617F mutation in ET patients wasassociated with PV-like phenotype. Our study also showed that the presence of the JAK2V617F mutation was associated with increased risk of thrombotic complications. Our results suggest that JAK2V617F mutation is associated with a more pronounced myeloproliferative phenotype in PMF patients. In a large number of Ph-negative MPN patients, our findings support that JAK2V617F mutation is associated with a more aggressive phenotype.