van Galen J C, Muris J J F, Giroth C P E, Vos W, Ossenkoppele G J, Meijer C J L M, Oudejans J J
Departments of Pathology and Haematology, VU Medical Centre, Amsterdam, The Netherlands.
Histopathology. 2008 Apr;52(5):578-84. doi: 10.1111/j.1365-2559.2008.02970.x. Epub 2008 Feb 23.
Tumour necrosis factor (TNF)-receptor associated factor 2 (TRAF2) is an adaptor molecule involved in nuclear factor (NF)-kappaB activation, which is characteristic of in vitro activated B-cell (ABC)-like diffuse large B-cell lymphomas (DLBCL) and may result in expression of anti-apoptotic genes and poor response to chemotherapy. TRAF2 also has direct anti-apoptotic properties via interference with the apoptosis signalling cascade. The aim was to determine whether TRAF2 is preferentially expressed in ABC-like DLBCL, and whether expression correlates with clinical outcome.
TRAF2 was expressed in nine of 20 tested ABC-like DLBCLs and in only one of 13 tested germinal centre B-lymphocyte (GCB)-like DLBCLs. High TRAF2 expression was correlated with high International Prognostic Index at time of presentation, high chance of relapse and short progression-free survival time in 44 tested DLBCLs. Furthermore, when analysis was restricted to ABC-like DLBCL only, TRAF2 expression was significantly associated with poor progression-free survival time.
TRAF2 might be involved in activation of NF-kappaB in a subset of ABC-like DLBCL, and its expression is associated with a particularly poor outcome in primary nodal DLBCL patients. Because of its possible effect on to chemotherapy resistance, resistance, TRAF2 might be an attractive candidate as a molecular target for TRAF2+ DLBCL.
肿瘤坏死因子(TNF)受体相关因子2(TRAF2)是一种衔接分子,参与核因子(NF)-κB的激活,这是体外活化B细胞(ABC)样弥漫性大B细胞淋巴瘤(DLBCL)的特征,可能导致抗凋亡基因的表达以及对化疗反应不佳。TRAF2还通过干扰凋亡信号级联反应具有直接的抗凋亡特性。目的是确定TRAF2是否在ABC样DLBCL中优先表达,以及其表达是否与临床结果相关。
在20例检测的ABC样DLBCL中有9例表达TRAF2,而在13例检测的生发中心B淋巴细胞(GCB)样DLBCL中只有1例表达。在44例检测的DLBCL中,TRAF2高表达与就诊时的高国际预后指数、高复发几率和短无进展生存期相关。此外,当仅对ABC样DLBCL进行分析时,TRAF2表达与无进展生存期差显著相关。
TRAF2可能参与了一部分ABC样DLBCL中NF-κB的激活,其表达与原发性淋巴结DLBCL患者的特别差的预后相关。由于其可能对化疗耐药产生影响,TRAF2可能是TRAF2+ DLBCL分子靶点的一个有吸引力的候选者。