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

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Şahin E., Yonal-Hindilerden I., Hindilerden F., Aday A., Nalçaci M.

Turkish journal of medical sciences, vol.52, pp.150-165, 2022 (SCI-Expanded) identifier identifier identifier identifier

  • Publication Type: Article / Article
  • Volume: 52
  • Publication Date: 2022
  • Doi Number: 10.3906/sag-2103-247
  • Journal Name: Turkish journal of medical sciences
  • Journal Indexes: Science Citation Index Expanded (SCI-EXPANDED), Scopus, Academic Search Premier, CAB Abstracts, EMBASE, MEDLINE, Veterinary Science Database, TR DİZİN (ULAKBİM)
  • Page Numbers: pp.150-165
  • Keywords: polycthemia vera, essential thrombocythemia, primary myelofibrosis, Philadelphia-negative myeloproliferative neoplasms, JAK2 V617F MUTATION, ESSENTIAL THROMBOCYTHEMIA, PRIMARY MYELOFIBROSIS, ALLELE BURDEN, JAK2-V617F MUTATION, JAK2(V617F) MUTATION, LABORATORY FINDINGS, POLYCYTHEMIA-VERA, RISK, DISORDERS
  • Istanbul University Affiliated: Yes


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.