Role of activation-induced cytidine deaminase in the progression of follicular lymphoma

Cancer Sci. 2012 Mar;103(3):415-21. doi: 10.1111/j.1349-7006.2011.02186.x. Epub 2012 Jan 17.

Abstract

Activation-induced cytidine deaminase (AID/AICDA) is required for somatic hypermutation and class-switch recombination of the immunoglobulin gene, and for c-myc translocation of germinal center-derived B-cell lymphoma. In the present study, we attempted to clarify the significance of AID associated with c-myc in the progression of follicular lymphoma (FL) using RT-PCR and quantitative real-time PCR. Tissues from the patients with grade 3 FL expressed relatively higher levels of c-myc and AID. The samples taken from a patient with FL who died within 2 years after the start of treatment showed either no or low expression of AID, despite expressing high levels of c-myc. In order to examine the role of AID expression in rapidly progressive FL, the full-length AID transcript was transfected into AID-negative cell lines established from different patients with rapidly progressive FL. This led to the establishment of AID-expressing transfectants with a low proliferation rate and a significantly increased incidence of G(0)/G(1) arrest compared with controls. Our results indicate that AID may act as a negative regulator of cell survival in FL when sufficient c-myc is expressed. Switch-off or low expression of AID after c-myc amplification may correlate with the clinical outcomes of FL.

MeSH terms

  • AICDA (Activation-Induced Cytidine Deaminase)
  • Adult
  • Aged
  • Blotting, Western
  • Cell Proliferation
  • Cytidine Deaminase / genetics
  • Cytidine Deaminase / metabolism*
  • Disease Progression
  • Enzyme Activation
  • Female
  • Gene Expression Profiling
  • Humans
  • Immunohistochemistry
  • Lymphoma, Follicular / genetics
  • Lymphoma, Follicular / metabolism*
  • Lymphoma, Follicular / pathology
  • Male
  • Middle Aged
  • Proto-Oncogene Proteins c-myc / genetics
  • Proto-Oncogene Proteins c-myc / metabolism*
  • Real-Time Polymerase Chain Reaction
  • Reverse Transcriptase Polymerase Chain Reaction
  • Transfection

Substances

  • MYC protein, human
  • Proto-Oncogene Proteins c-myc
  • AICDA (Activation-Induced Cytidine Deaminase)
  • Cytidine Deaminase