Hosoi Hiroki, Imadome Ken-Ichi, Tamura Shinobu, Kuriyama Kodai, Murata Shogo, Yamashita Yusuke, Mushino Toshiki, Oiwa Takehiro, Kobata Hiroshi, Nishikawa Akinori, Nakakuma Hideki, Hanaoka Nobuyoshi, Isobe Yasushi, Ohshima Kouichi, Sonoki Takashi
Hematology/Oncology, Wakayama Medical University, Japan.
Division of Advanced Medicine for Virus Infections, National Research Institute for Child Health and Development, Japan.
Leuk Res. 2017 Apr;55:1-5. doi: 10.1016/j.leukres.2017.01.022. Epub 2017 Jan 15.
We managed a patient with an Epstein-Barr virus-associated T-cell lymphoblastic lymphoma. Mediastinal tumor cells at initial admission were positive for CD4, CD8, and TdT. Interestingly, a lymph node at necropsy was compatible for a CD4-positive peripheral T-cell lymphoma without CD8 and TdT expression, suggesting a different phenotype from the mediastinal tumor. Tumor cells in pleural effusion continued to proliferate in in vitro and were designated as WILL4. WILL4 cells were positive for CD3, CD4, CD8, CD21, T-cell receptor (TcR) αβ, and TdT, indicating a similar phenotype to thymocytes. Southern blot analyses showed that the pleural tumor and WILL4 cells shared a TcR gene rearrangement, and that both contained a clonal EBV genome in an episomal form. RT-PCR showed that EBNA1 and LMP1 were expressed in the fresh tumor and WILL4 cells. Southern blot analyses revealed that WILL4 cells were susceptible to EBV infection in vitro using B95-8 supernatant. Anti-CD21 antibody inhibited in vitro infection of EBV, suggesting that CD21 plays a role in EBV infection into WILL4 cells. In vitro infection of EBV did not affect latent gene expression in WILL4 cells. WILL4 is a useful tool for analyzing the roles of EBV in onocogenesis in immature T-lymphoid malignancies.
我们诊治了一名患有爱泼斯坦-巴尔病毒相关T细胞淋巴母细胞淋巴瘤的患者。初次入院时纵隔肿瘤细胞CD4、CD8和末端脱氧核苷酸转移酶(TdT)呈阳性。有趣的是,尸检时的一个淋巴结符合CD4阳性外周T细胞淋巴瘤,无CD8和TdT表达,提示其表型与纵隔肿瘤不同。胸腔积液中的肿瘤细胞在体外持续增殖,被命名为WILL4。WILL4细胞CD3、CD4、CD8、CD21、T细胞受体(TcR)αβ和TdT呈阳性,表明其表型与胸腺细胞相似。Southern印迹分析显示,胸腔肿瘤细胞和WILL4细胞具有相同的TcR基因重排,且两者均含有游离形式的克隆性EBV基因组。逆转录聚合酶链反应(RT-PCR)显示,新鲜肿瘤细胞和WILL4细胞中EBNA1和LMP1均有表达。Southern印迹分析显示,使用B95-8上清液时,WILL4细胞在体外易受EBV感染。抗CD21抗体可抑制EBV的体外感染,提示CD21在EBV感染WILL4细胞中起作用。EBV的体外感染不影响WILL4细胞中的潜伏基因表达。WILL4是分析EBV在未成熟T淋巴细胞恶性肿瘤发生中作用的有用工具。