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 -negative myeloproliferative 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 410 Ph-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). Two hundred and twenty-eight 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) level, higher leukocyte and platelet count 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 was associated 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.

The impact of JAK2V617F allele burden on clinical course in Philadelphia-negative (Ph-negative) myeloproliferative neoplasms (MPNs) is not clear. We analyzed the clinical impact of JAK2V617F allele burden in a relatively large patient series of Ph-negative MPNs with long term follow-up. 228 patients with Ph-negative MPNs-118 essential thrombocythemia (ET), 84 primary myelofibrosis (PMF) and 26 polycythemia vera (PV)- were analyzed. JAK2 MutaScreen assay was used to quantify JAK2V617F allele burden in genomic DNA. In PV, high JAK2V617F allele burden was associated with a trend towards inferior OS. In ET, high JAK2V617F allele burden was associated with lower Hgb and hematocrit (Hct) levels, higher lactate dehydrogenase (LDH) levels, greater spleen size, increased bleeding and death rate. In PMF, high JAK2V617F allele burden was associated with higher leukocyte counts and greater spleen size. In the entire cohort, high allele burden was associated with higher leukocyte and lower platelet counts, higher LDH levels, greater spleen size, higher percentage of bleeding events, higher death rate and inferior OS. Our results remark high JAK2V617F allele burden is associated with more severe disease in PV and ET. In PMF, high JAK2V617F allele burden was associated with more pronounced myeloproliferative phenotype. In Ph-negative MPN, high allele burden was associated with more aggressive phenotype. Our data with long follow-up period support JAK2V617F allele burden may be a marker for predicting clinical phenotype in Ph-negative MPNs.

Aim: In critical cases, electrolyte disturbances such as hypophosphatemia have been shown to be associated with mortality and in our study, we aimed to examine the relationship between hypophosphatemia, a symptom disorder with COVID-19, and death. Material and Methods: This study is a retrospective, cross-sectional investigation that encompasses patients diagnosed with COVID-19 and subsequently admitted for treatment at our hospital. Based on their serum phosphate levels, the patients were bifurcated into two distinct categories: those with serum phosphate levels below 2.5 mg/dl, classified as hypophosphatemic, and those with levels above this benchmark, categorized as non-hypophosphatemic. The comparisons drawn between these two cohorts were facilitated using a range of statistical methodologies, and the resulting findings were subsequently analyzed and interpreted within this framework. Results: Compared to the hypophosphatemia group, the diagnoses of DM (p<0.001) and CKD (p=0.015) were statistically significantly higher in the group without hypophosphatemia. A statistically significant difference was found between phosphorus groups and mortality and length of stay (p<0.001). In addition, age and length of hospitalization were found to be statistically significantly higher in those who died compared to those who were alive (p<0.001; p=0.002). Conclusions: Hypophosphatemia has been shown to be associated with mortality in patients with COVID-19, as in many studies and in our study, and it may be a biomarker in predicting severe disease.