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

Role of activation‐induced cytidine deaminase in the progression of follicular lymphoma
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激活诱导的胞苷脱氨酶在滤泡性淋巴瘤进展中的作用

DOI:
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发表时间:
2012
期刊:
影响因子:
5.7
通讯作者:
M. Yasukawa
M. Yasukawa
中科院分区:
医学2区
文献类型:
--
作者:
Hisaharu Shikata;Y. Yakushijin;Natsuki Matsushita;A. Sakai;A. Sugita;N. Nakamura;J. Yamanouchi;T. Azuma;T. Hato;M. Yasukawa

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激活诱导的胞苷脱氨酶 (AID/AICDA) 是免疫球蛋白基因的体细胞超突变和类别转换重组以及生发中心来源的 B 细胞淋巴瘤的 c-myc 易位所必需的。在本研究中,我们试图利用 RT-PCR 和定量实时 PCR 阐明与 c-myc 相关的 AID 在滤泡性淋巴瘤 (FL) 进展中的重要性。 3 级 FL 患者的组织表达相对较高水平的 c-myc 和 AID。从开始治疗后 2 年内死亡的 FL 患者采集的样本显示,尽管 c-myc 表达水平很高,但 AID 没有表达或表达较低。为了检查 AID 表达在快速进展性 FL 中的作用,将全长 AID 转录物转染到由不同快速进展性 FL 患者建立的 AID 阴性细胞系中。这导致表达 AID 的转染子的建立,与对照相比,其增殖率低且 G0/G1 停滞发生率显着增加。我们的结果表明,当表达足够的 c-myc 时,AID 可能充当 FL 细胞存活的负调节因子。 c-myc 扩增后 AID 的关闭或低表达可能与 FL 的临床结果相关。 (《癌症科学》2012 年;103:415–421)
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)
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