ABSTRACT
Background: Five epigenetic regulator mutations are considered in myeloproliferative neoplasms (MPN) that have prognostic and therapeutic values. Objective: We aimed to evaluate these mutations in MPNs among the Iranian population. Methods: We selected 5 mutations in 4 epigenetic regulatory genes [TET2, DNMT3A, IDH1 (rs147001633&rs121913499), and JAK2)] and evaluated 130 patients with MPNs including 78 Philadelphia chromosome negative (49 ETs, 20 PVs, and 9 PMFs) and 52 Philadelphia chromosome-positive patients as well as 51 healthy controls. Results: Eight patients (6.5%) carried the DNMT3A mutation, 35 (27%) were positive for TET2 mutation and 64 (49.3%) had the JAK2V617F mutation. In the healthy controls, 16 (31.4%) cases had the TET2 mutation (15 Heterozygote + 1 Homozygote) and one had heterozygote JAK2 mutation. There was no statistically significant difference between patient groups for any of these mutations, except for JAK2. The JAK2 mutation rate was 18 (90%), 25 (51%), 7 (77.8%), 14 (26.9%) in polycythemia vera, essential thrombocythemia, primary myelofibrosis, and chronic myelocytic leukemia, respectively. Patients aged 60 and older were more likely to carry the TET2 mutation (23% vs. 39% in younger and older than 60 years old individuals, p=0.025). IDH1 was not detected at all and PV had the highest TET2 mutation 7(35%). Two PMF patients had a history of bone marrow transplantation that were negative for IDH1and DNMT3A and one was positive for TET2 mutation. Conclusion: In the normal Iranian population, the heterozygote form of TET2 mutation is significant, especially in the elderly. No association was found between JAK2 and TET2 mutations. Both of them are more prevalent in the age group of 60 years and older. DNMT3A mutation has a low prevalence and occurs in both positive and negative MPNs.
