Aberrant expression of the CHFR prophase checkpoint gene in human B-cell non-Hodgkin lymphoma

Leuk Res. 2015 May;39(5):536-43. doi: 10.1016/j.leukres.2015.02.007. Epub 2015 Feb 25.


Checkpoint with FHA and Ring Finger (CHFR) is a checkpoint protein that reportedly initiates a cell cycle delay in response to microtubule stress during prophase in mitosis, which has become an interesting target for understanding cancer pathogenesis. Recently, aberrant methylation of the CHFR gene associated with gene silencing has been reported in several cancers. In the present study, we examined the expression of CHFR in B-cell non-Hodgkin lymphoma (B-NHL) in vitro and in vivo. Our results showed that the expression level of CHFR mRNA and protein was reduced in B-NHL tissue samples and B cell lines. Furthermore, CHFR methylation was detected in 39 of 122 B-NHL patients, which was not found in noncancerous reactive hyperplasia of lymph node (RH) tissues. CHFR methylation correlated with the reduced expression of CHFR, high International Prognostic Index (IPI) scores and later pathologic Ann Arbor stages of B-NHL. Treatment with demethylation reagent, 5-Aza-dC, could eliminate the hypermethylation of CHFR, enhance CHFR expression and cell apoptosis and inhibit the cell proliferation of Raji cells, which could be induced by high expression of CHFR in Raji cells. Our results indicated that aberrant methylation of CHFR may be associated with the pathogenesis, progression for B-NHL, which might be a novel molecular marker as prognosis and treatment for B-NHL.

Keywords: B-cell non-Hodgkin lymphoma; CHFR; Methylation; Raji cell.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Cell Cycle Checkpoints / genetics
  • Cell Cycle Proteins / genetics*
  • Cell Line, Tumor
  • Child
  • Child, Preschool
  • DNA Methylation
  • Female
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Lymphoma, B-Cell / genetics*
  • Lymphoma, B-Cell / pathology
  • Male
  • Middle Aged
  • Neoplasm Proteins / genetics*
  • Poly-ADP-Ribose Binding Proteins
  • Prophase / genetics
  • Ubiquitin-Protein Ligases
  • Young Adult


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