High IDH1 expression is associated with a poor prognosis in cytogenetically normal acute myeloid leukemia

Int J Cancer. 2015 Sep 1;137(5):1058-65. doi: 10.1002/ijc.29395. Epub 2015 Jan 13.

Abstract

The prognostic value of IDH1 mutations has been systematically evaluated in acute myeloid leukemia (AML) patients recently. However, the role of IDH1 expression in AML is still under exploration. To investigate the clinical significance, we analyzed the IDH1/2 expression in 320 patients with cytogenetically normal AML (CN-AML) by quantitative real-time reverse-transcription polymerase chain reaction. High expression of IDH1 was predominant in patients with FLT3-ITD and DNMT3A mutations and less prevalent in cases with CEBPA double allele mutations. Strong association was observed between high IDH1 expression and low expression of microRNA 181 family. Prognosis was adversely affected by high IDH1 expression, with shorter overall survival and event-free survival in the context of clinical characteristics, including age, WBC count, and gene mutations of NPM1, FLT3-ITD, CEBPA, IDH1, IDH2 and DNMT3A in CN-AML. Moreover, the clinical outcome of IDH1 expression in terms of overall survival, event-free survival and complete remission rate still remained in multivariate models in CN-AML. Importantly, the prognostic value was validated using the published microarray data from 79 adult patients treated according to the German AMLCG-1999 protocol. Our results demonstrated that high IDH1 expression is associated with a poor prognosis of CN-AML.

Keywords: acute myeloid leukemia; gene expression; isocitrate dehydrogenase 1; prognosis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Female
  • Gene Expression Profiling
  • Gene Expression Regulation, Leukemic
  • Humans
  • Isocitrate Dehydrogenase / genetics*
  • Karyotype
  • Leukemia, Myeloid, Acute / genetics*
  • Leukemia, Myeloid, Acute / pathology*
  • Male
  • Middle Aged
  • Mutation
  • Nucleophosmin
  • Prognosis
  • Survival Analysis
  • Up-Regulation*
  • Young Adult

Substances

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