Genetic Polymorphism Study of IDH 1/2 and TET2 Genes in Acute Myeloid leukemia Patients

Abstract

Background and Objective: Isocitrate dehydrogenase genes ( IDH1 and IDH2 ) encode important enzymes that play pivotal role in cellular metabolism. Mutations in TET2 have been demonstrated to contribute to DNA hypermethylation, either expression of mutant IDH1 / 2 or TET2 resulted in poor cell differentiation and epigenetic alterations in hematopoietic cells, suggesting a sharing of the oncogenetic impact. In this study, we investigated the frequency of genetic alterations in IDH1/2 and TET2 genes in Egyptian cohort of adult patients with de novo AML, and the association of IDH1 / 2 and TET2 genetic Polymorphism with AML prognostic criteria and explore prognostic molecular markers with clinical outcome. Methods: The SNP assay for IDH1 , IDH2 and TET2 genes polymorphism tested with RT-PCR included three polymorphisms that are rs121913500, rs121913503, and rs2454206 respectively, were tested on 141 adult Egyptian patients fulfilling the AML diagnostic criteria. Result: The incidence of IDH mutations is 11/141 (7.8%); 5/141 (3.5%) IDH1 mutant and 6/141 (4.3%) IDH2 mutant. And the incidence of TET2 mutations is 72/141 (51.1%); 15/141 (10.7%) homozygous mutation and 57/141 (40.4%) heterozygous mutations. IDH1 , IDH2 and TET2 genes mutations with DFS and OS in AML patients were not significantly correlated. Conclusions: TET2 SNP is common in Egyptian AML patients. Further research on IDH, TET2 and their relationships to other hematological malignancies and leukemogenesis transformation is advised and a study of a larger number of cases is needed for potential statistical significance.