Mutation Analysis of IDH1/2 Genes in Unselected De novo Acute Myeloid Leukaemia Patients in India - Identification of A Novel IDH2 Mutation

Asian Pac J Cancer Prev. 2015;16(9):4095-101. doi: 10.7314/apjcp.2015.16.9.4095.

Abstract

IDH1/2 mutations which result in alternation in DNA methylation pattern are one of the most common methylation associated mutations in Acute myeloid leukaemia. IDH1/2 mutations frequently associated with higher platelet level, normal cytogentics and NPM1 mutations. Here we analyzed IDH1/2 mutations in 200 newly diagnosed unselected Indian adult AML patients and investigated their correlation with clinical, cytogenetic parameters along with cooperating NPM1 mutation. We detected 5.5% and 4% mutations in IDH1/2 genes, respectively. Except IDH2 c.515_516GG>AA mutation, all the other identified mutations were reported mutations. Similar to reported c.515G>A mutation, the novel c.515_516GG>AA mutation replaces 172nd arginine to lysine in the active site of the enzyme. Even though there was a preponderance of IDH1/2 mutations in NK-AML, cytogenetically abnormal patients also harboured IDH1/2 mutations. IDH1 mutations showed significant higher platelet count and NPM1 mutations. IDH2 mutated patients displayed infrequent NPM1 mutations and lower WBC count. All the NPM1 mutations in the IDH1/2 mutated cases showed type A mutation. The present data suggest that IDH1/2 mutations are associated with normal cytogenetics and type A NPM1 mutations in adult Indian AML patients.

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Cohort Studies
  • DNA Mutational Analysis
  • Female
  • Follow-Up Studies
  • Genotype
  • Humans
  • In Situ Hybridization, Fluorescence
  • India
  • Isocitrate Dehydrogenase / genetics*
  • Leukemia, Myeloid, Acute / genetics*
  • Leukemia, Myeloid, Acute / pathology
  • Male
  • Middle Aged
  • Mutation / genetics*
  • Neoplasm Staging
  • Nuclear Proteins / genetics
  • Nucleophosmin
  • Prognosis
  • Young Adult

Substances

  • NPM1 protein, human
  • Nuclear Proteins
  • Nucleophosmin
  • IDH2 protein, human
  • Isocitrate Dehydrogenase
  • IDH1 protein, human