title: Role of activation-induced cytidine deaminase in the progression of follicular lymphoma.
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.
authors.affiliation: Department of Bioregulatory Medicine, Ehime University Hospital, Ehime University Graduate School of Medicine, Toon, Japan.
authors.forename: Hisaharu
authors.initials: H
authors.lastname: Shikata
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Yakushijin
authors.forename: Natsuki
authors.initials: N
authors.lastname: Matsushita
authors.forename: Akira
authors.initials: A
authors.lastname: Sakai
authors.forename: Atsuro
authors.initials: A
authors.lastname: Sugita
authors.forename: Naoya
authors.initials: N
authors.lastname: Nakamura
authors.forename: Jun
authors.initials: J
authors.lastname: Yamanouchi
authors.forename: Taichi
authors.initials: T
authors.lastname: Azuma
authors.forename: Takaaki
authors.initials: T
authors.lastname: Hato
authors.forename: Masaki
authors.initials: M
authors.lastname: Yasukawa
mesh_terms: D000328:Adult; D000368:Aged; D015153:Blotting, Western; D049109:Cell Proliferation; D003564:Cytidine Deaminase / Q000235:genetics / Q000378:metabolism*; D018450:Disease Progression; D004789:Enzyme Activation; D005260:Female; D020869:Gene Expression Profiling; D006801:Humans; D007150:Immunohistochemistry; D008224:Lymphoma, Follicular / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D016271:Proto-Oncogene Proteins c-myc / Q000235:genetics / Q000378:metabolism*; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014162:Transfection; D000098830:AICDA (Activation-Induced Cytidine Deaminase)
chemical_list: C489427:MYC protein, human; D016271:Proto-Oncogene Proteins c-myc; D000098830:AICDA (Activation-Induced Cytidine Deaminase); D003564:Cytidine Deaminase