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

• Published in: Cancer science Vol. 103; no. 3; pp. 415 - 421
• Main Authors: Shikata, Hisaharu, Yakushijin, Yoshihiro, Matsushita, Natsuki, Sakai, Akira, Sugita, Atsuro, Nakamura, Naoya, Yamanouchi, Jun, Azuma, Taichi, Hato, Takaaki, Yasukawa, Masaki
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Publishing Ltd 01.03.2012
• Subjects: Activation-induced cytidine deaminase; Adult; Aged; Blotting, Western; c-Myc protein; Cancer; Cell Proliferation; Cell survival; Class switching; Cytidine Deaminase - genetics; Cytidine Deaminase - metabolism; Disease Progression; double prime B-cell lymphoma; Enzyme Activation; Female; Gene Expression Profiling; Humans; Immunoglobulins; Immunohistochemistry; Lymphoma, Follicular - genetics; Lymphoma, Follicular - metabolism; Lymphoma, Follicular - pathology; Male; Middle Aged; Original; Polymerase chain reaction; Proto-Oncogene Proteins c-myc - genetics; Proto-Oncogene Proteins c-myc - metabolism; Real-Time Polymerase Chain Reaction; Recombination; Reverse Transcriptase Polymerase Chain Reaction; somatic hypermutation; Transcription; Transfection; Translocation
• ISSN: 1347-9032; 1349-7006; 1349-7006
• DOI: 10.1111/j.1349-7006.2011.02186.x

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 G0/G1 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. (Cancer Sci 2012; 103: 415–421)