Department of Pathology, Hallym University Sacred Heart Hospital, Anyang, Republic of Korea.
Department of Pathology, College of Medicine, Seoul National University, Seoul, Republic of Korea.
Mod Pathol. 2016 Nov;29(11):1313-1323. doi: 10.1038/modpathol.2016.128. Epub 2016 Jul 29.
PELI is a family of E3 ubiquitin ligases that regulate protein activity through a post-translational modification, ubiquitination. While PELI1 has been found to play a pivotal role in inflammatory processes through the activation of Toll-like receptor signaling and the NF-kB pathway, the role of PELI1 in oncogenesis has not been the subject of much investigation. We aimed to explore PELI1 expression in various malignant lymphomas and identify clinicopathologic significance. Immunohistochemistry for PELI1 was performed on a total of 502 cases, including 406 B-cell, 76 T or NK-cell, and 20 Hodgkin lymphomas. High expression of PELI1 was found in high-grade B-cell lymphoma cases such as diffuse large B-cell lymphoma, Burkitt lymphoma, and plasmablastic lymphoma, whereas low-grade B-cell lymphoma, T/NK-cell lymphoma, and Hodgkin lymphoma cases showed very low levels of expression. In vitro cell line studies, the results of western blot, and RT-PCR were concordant with those of the immunohistochemical results; RL7, Pfeiffer, SUDHL-2, DOHH2, and Ramos cell lines showed high levels of PELI1 protein and mRNA expression. In 182 diffuse large B-cell lymphoma, PELI1 expression was positively correlated with the expression of MYC, BCL6, BCL2, and MUM1 (Spearman's ρ=0.427, 0.507, 0.246, and 0.137, respectively; P<0.001, <0.001, 0.001, and 0.066, respectively). In diffuse large B-cell lymphoma, high expression of PELI1 was associated with frequent bone marrow involvement (P=0.013) and shorter relapse-free survival (P=0.002). Our results suggest that PELI1 might participate in B-cell maturation or oncogenic activation of aggressive B-cell lymphomas, both during and after germinal center stages.
PELI 是一类 E3 泛素连接酶，通过翻译后修饰——泛素化来调节蛋白质活性。虽然已经发现 PELI1 通过激活 Toll 样受体信号和 NF-kB 途径在炎症过程中发挥关键作用，但 PELI1 在肿瘤发生中的作用尚未得到广泛研究。我们旨在探讨 PELI1 在各种恶性淋巴瘤中的表达情况，并确定其临床病理意义。我们对总共 502 例病例进行了 PELI1 的免疫组织化学检测，其中包括 406 例 B 细胞、76 例 T/NK 细胞和 20 例霍奇金淋巴瘤。高表达 PELI1 见于高级别 B 细胞淋巴瘤，如弥漫性大 B 细胞淋巴瘤、伯基特淋巴瘤和浆母细胞淋巴瘤，而低级别 B 细胞淋巴瘤、T/NK 细胞淋巴瘤和霍奇金淋巴瘤则表达水平非常低。体外细胞系研究、western blot 和 RT-PCR 的结果与免疫组织化学结果一致；RL7、Pfeiffer、SUDHL-2、DOHH2 和 Ramos 细胞系表现出高水平的 PELI1 蛋白和 mRNA 表达。在 182 例弥漫性大 B 细胞淋巴瘤中，PELI1 的表达与 MYC、BCL6、BCL2 和 MUM1 的表达呈正相关（Spearman's ρ=0.427、0.507、0.246 和 0.137，分别；P<0.001、<0.001、0.001 和 0.066，分别）。在弥漫性大 B 细胞淋巴瘤中，PELI1 的高表达与频繁的骨髓受累（P=0.013）和较短的无复发生存时间（P=0.002）相关。我们的结果表明，PELI1 可能参与 B 细胞成熟或生发中心阶段前后侵袭性 B 细胞淋巴瘤的致癌激活。
