Potential application of IDH1 and IDH2 mutations as prognostic indicators in non-promyelocytic acute myeloid leukemia: a meta-analysis

Leuk Lymphoma. 2012 Dec;53(12):2423-9. doi: 10.3109/10428194.2012.695359. Epub 2012 Jun 18.

Abstract

Recurrent mutations of isocitrate dehydrogenase isoforms 1 and 2 (IDH1 and IDH2) have recently been studied in adult patients with acute myeloid leukemia (AML). A meta-analysis was performed to demonstrate their controversial prognostic impacts. The associations of IDH1 or IDH2 mutations with other molecular abnormalities were also investigated. In patients with AML, IDH1/2 mutations were significantly associated with normal karyotype and isolated trisomy 8 (p < .05). After adjusting for well-studied prognostic factors, IDH1 mutation seems to be associated with subtle but significantly inferior event-free survival (EFS) (p = 0.02) and possible adverse overall survival (OS) (p = 0.13) in patients with AML, especially in the favorable genotype subset with mutated NPM1 but without FLT3-ITD mutation (p < 0.05). Longer OS (p = 0.01) and better EFS tendency (p = 0.18) are implicated in patients with IDH2 mutations, which suggests that IDH2 mutations appear to confer a favorable prognosis. Moreover, IDH1 and IDH2 mutations may play a more important role in abnormal cytogenetics subgroups such as isolated trisomy 8. Screening of IDH1/2 mutations could help to identify patients at high risk within some subsets of AML.

Publication types

  • Meta-Analysis
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Biomarkers, Tumor / genetics*
  • Disease-Free Survival
  • Female
  • Humans
  • Isocitrate Dehydrogenase / genetics*
  • Leukemia, Myeloid, Acute / enzymology
  • Leukemia, Myeloid, Acute / genetics*
  • Leukemia, Myeloid, Acute / pathology
  • Male
  • Mutation*
  • Nuclear Proteins / genetics
  • Nucleophosmin
  • Prognosis
  • Regression Analysis

Substances

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