Detection of mutations in the isocitrate dehydrogenase genes (IDH1/IDH2) using castpcrtm in patients with aml and their clinical impact in Mexico city

Abstract

Objective: Approximately 40–50% of patients with acute myeloid leukaemia (AML) have been reported to present with a normal karyotype and a variable disease-free period, most likely due to the molecular heterogeneity presented by these patients. A variety of mutations have been identified at the molecular level, such as those in the IDH1/2 gene, which causes a gain of function of the isocitrate dehydrogenase enzyme, generating high levels of the (R)-2- hydroxyglutarate oncometabolite, which competitively inhibits dioxygenase enzymes. Therefore, the objective of this study was to evaluate the incidence of IDH1/2 gene mutations in AML patients and their impact on survival. Materials and methods: A total of 101 patients with a diagnosis of AML were included; mononuclear cells were obtained for DNA extraction and purification. Mutations were detected using TaqMan™ competitive allele-specific probes (castPCR™). Overall survival curves were plotted using IBM SPSS Statistics 23 software. Results: The frequency of IDH gene mutations was 19.8%. For the IDH1 gene, 13.8% of the mutations identified included R132H, V178I, G105G and R132C. The frequency of mutations of the IDH2 gene was 5.9%; the variants included R172K and R140Q. The mean survival time in patients without IDH1 gene mutations was 173.15 days (120.20– 226.10), while the mean survival time for patients with mutations was 54.95 days (9.7– 100.18), p = 0.001. Conclusion: The frequency of IDH1 and IDH2 gene mutations in the sample was similar to that reported in other studies. The analysis of these mutations in AML patients is of great importance as a prognostic factor due to their impact on survival and their use as potential therapeutic targets or as targets of inhibitors of IDH1(Ivosidenib, Tibsovo) and IDH2 (Enasidenib, Idhifa).