CHFR hypermethylation, a frequent event in acute myeloid leukemia, is independently associated with an adverse outcome

Genes Chromosomes Cancer. 2016 Feb;55(2):158-68. doi: 10.1002/gcc.22322. Epub 2015 Nov 6.


The CpG island of the promoter region of the checkpoint with fork-head associated and ring finger gene (CHFR), a mitotic checkpoint gene with tumor-suppressor functions, is hypermethylated in various human cancers. The objective of this study was to evaluate the frequency of aberrant CHFR promoter methylation in acute myeloid leukemia (AML) patients in an attempt to improve prognostication. CHFR promoter methylation levels were analyzed in 358 newly diagnosed AML cases and 30 healthy donors by the use of quantitative methylation-specific polymerase chain reaction. In addition, we analyzed possible association between CHFR hypermethylation and hematological characteristics, chromosome abnormalities, genetic mutations, and survival. Hypermethylation of the CHFR promoter was observed in 24% (85 of 358) AML patients, but not in healthy individuals. CHFR hypermethylation correlated significantly with SRSF2 and DNMT3A mutations. Patients with hypermethylation exhibited lower overall survival and shorter relapse-free survival than nonmethylated cases. In multivariate analysis, CHFR hypermethylation was an independent factor predicting poor overall survival but not relapse-free survival. In conclusion, hypermethylation of the CHFR promoter, frequent in AML, is associated with adverse outcome, and can thus be used for risk stratification.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Cell Cycle Proteins / genetics*
  • Child
  • DNA Copy Number Variations
  • DNA Methylation*
  • Female
  • Humans
  • Leukemia, Myeloid, Acute / genetics*
  • Leukemia, Myeloid, Acute / pathology*
  • Male
  • Middle Aged
  • Mutation
  • Neoplasm Proteins / genetics*
  • Poly-ADP-Ribose Binding Proteins
  • Prognosis
  • Promoter Regions, Genetic
  • Survival Analysis
  • Ubiquitin-Protein Ligases
  • Young Adult


  • Cell Cycle Proteins
  • Neoplasm Proteins
  • Poly-ADP-Ribose Binding Proteins
  • CHFR protein, human
  • Ubiquitin-Protein Ligases