<p>Detection Of Mutations In The Isocitrate Dehydrogenase Genes (IDH1/IDH2) Using castPCR^TM In Patients With AML And Their Clinical Impact In Mexico City</p>

Abstract

ObjectiveApproximately 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 methodsA 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.ResultsThe 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.ConclusionThe 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).

First inter-institutional consensus on chronic myeloproliferative neoplasms

“…the detection of the JAK2 V617F mutation can be performed in peripheral blood (SP) or bone marrow (MO) by polymerase chain reaction (PCR) techniques, such as allele specific PCR or RFLP (polymorphism in the length of restriction fragments), by DNA sequencing or by Cast-PCR Competitive allele-specific TaqMan PCR 4 .…”

“…The percentage of the JAK2 V617F allele is evaluated in relation to the total copies of the JAK2 gene. The usefulness of allelic load measurement in the stratification of patients in risk groups and therapeutic management has not yet been defined 3,4 .…”

“…In addition, the data produced by NGS are not easy for routine clinical analysis 21 . Among the driver alterations that we have analyzed in our team and published through this strategy, are mutations in the IDH1/IDH2 genes in patients with LAM 22 .…”

High expression levels and the C3435T SNP of the ABCB1 gene are associated with lower survival in adult patients with acute myeloblastic leukemia in Mexico City

“…At the end of the study, the patients started the maintenance phase by administering weekly mercaptopurine and methotrexate for a duration of 2 years. In case of relapse to bone marrow, the patients received rescue therapy [ 20 ]. The evaluation of the minimal residual disease was evaluated at the hematological level.…”

Clinical impact of IDH1 mutations and MGMT methylation in adult glioblastoma

“…Competitive allele-specific TaqMan PCR (Cast-PCR) technology was used to detect IDH1 mutation as it is sensitive, specific and fast method for detection of mutant allele since it permits not only the discriminating amplification of minor alleles, but it also blocks the amplification of non-mutant allele [20,21]. Qualitative assessment of six mutations within IDH1 mutation codon 132 (the 2 major R132H and R132C mutations, and 4 "IDH1-other": R132G, R132S, R132L, R132V), one within IDH1 codon 100 (R100Q), Amplification Refractory Mutation System (ARMS) PCR technology was combined to selectively identify the most frequent IDH1 R132H/R132C.…”