The Role of Activation-Induced Cytidine Deaminase (AID/AICDA) in the Progression of Follicular Lymphoma
Authors: Shikata Hisaharu , Yakushijin Yoshihiro , Matsushita Natsuki , Sakai Akira , Sugita Atsuro , Nakamura Naoya , Yamanouchi Jun , Azuma Taichi , Hato Takaaki , Yasukawa Masaki 
Published: October 2019

Abstract
Abstract 5234
Follicular lymphoma (FL), a entity with a cell origin in germinal center B lymphocytes, may develop into a progressive or transformed disease in some patients. This transformation is usually associated with acceleration of the clinical course. Transformed FLs generally retain the t(14;18) translocation, and it is believed that other genetic abnormalities are necessary in order for this transformation to occur. Secondary genetic events have been associated with this transformation such as c-myc amplification or mutation. Activation induced cytidine deaminase (AID/AICDA) is required for somatic hyper-mutation and class switch recombination of immunoglobulin gene, and also deeply involved in c-myc translocation of GCB-cell lymphoma. However, the role of AID in transformed FL has not been established. Here we tried to identify the significance of AID associated with c-myc in the progression of FL using mRNAs from tissue biopsy samples from patients with FL. The FLs we examined were divided into three groups: patients with grade 1–2 FL (n=15), patients with grade 3 FL who survived more than two years (n=14), and patients with rapidly progressive FL (RPFL) who died within two years after the start of treatment (n=6). AID and c-myc expression among those patients with FL were examined with RT-PCR and quantitative real-time PCR. Samples from the patients with grade 3 FL expressed relatively higher levels of the c-myc transcript than samples from the patients with grade 1–2 FL (p=.02) respectively. Additionally, nonsignificantly high levels of AID expression were observed in tissues from the patients with grade 3 FL. Interestingly, the samples taken from a patient with FL who died within two years after the start of treatment, showed either no or low expression of AID, despite expressing high levels of c-myc. These results suggested that overexpression of c-myc might be correlated with the biological transformation and clinical progression of FL; and also that AID might play a partial role in disease progression, and low expression of AID may be associated with the clinical features and outcome of patients with RPFL. In order to examine the role of AID expression in RPFL, the full-length AID gene was transfected into AID-negative and c-myc-positive cell lines established from patients with RPFL. AID-positive transfectants exhibited damping of cell proliferation proportional to the genetic level of AID expression, relative to the parental cells and the vector-only transfectants used as controls. Cell cycle analysis showed that the AID-positive transfectants had an increased cell population in G0/G1 phase and a reduced population in S phase, suggesting that G0/G1 arrest was responsible for the reduction in cell proliferation relative to the controls. These in vivo and in vitro findings suggest 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 be a potentially useful marker for prognostication of FL.

Disclosures:
No relevant conflicts of interest to declare.