Frequency of JAK2V617F Mutation Zygosity and Impact on Disease Outcome in MPN Patients.

Background: Myeloproliferative Neoplasm (MPN) is a clonal disorder of blood progenitor cells during haematopoiesis. JAK2V617F mutation represents one of the major identified genetic reasons of MPN disorder. It has been shown that JAK2V617F zygosity is associated with disease phenotype. However, studies showed variable findings regarding individual phenotype parameters and significance of effect.

Objectives: the aim of this study was to determine frequency of JAK2V617F zygosity and corresponding outcomes in this population.

Methods: This cross-section study recruited JAK2V617F-mutated polycythemia Vera (PV), essential thrombocythemia (ET), and myelofibrosis (MF) patients. DNA samples were extracted from peripheral blood and JAK2V617F zygosity was determined using ARMS-PCR method.

Results: A total of 162 patients (91 males and 71 females) were analysed. Of total, 131 (80.86 %) were heterozygous and 31 (19.14 %) were homozygous for JAK2V617F. homozygous characterized with higher age (P= 0.0153) and WBC count (P= < 0.0001). Among total MPN cases, the number of PV, ET, and MF patients was 102 (62.96%), 37 (22.84%), and 23 (14.2%) respectively. The frequency of homozygous cases was 20.6 %, 10.8 %, and 26.1 % for PV, ET, and MF patients respectively. No significant difference seen in age, BMI, and HCT between homozygous and heterozygous cases in all MPN groups. In ET group, homozygous patients showed significant HGB reduction (P= 0.0186) and PLT increase (P= 0.0034) compared with heterozygous patients. WBC count in homozygous patients was significantly higher than heterozygous in PV (P= 0.0071), ET (P= <0.0001), and MF (P= 0.07) patients.

Conclusion: JAK2V617F zygosity is useful marker in determining disease severity and can be used for prediction of prognosis in MPN patients. ARMS-PCR is simple, easy, and useful technique in determining zygosity of mutations and does not need to advanced laboratory resources. We recommend including zygosity in laboratory reports when conducting JAK2V617F using ARMS-PCR technique.