van Doorn Remco, Dijkman Remco, Vermeer Maarten H, Starink Theo M, Willemze Rein, Tensen Cornelis P
Department of Dermatology, Vrije Universiteit Medical Center, 1081 HV Amsterdam, the Netherlands.
Cancer Res. 2002 Oct 1;62(19):5389-92.
Defective apoptosis signaling has been implicated in the pathogenesis of primary cutaneous T-cell lymphomas (CTCLs), a group of malignancies derived from skin-homing T cells. An important mediator of apoptosis in T cells is the Fas receptor. We identified a novel splice variant of the Fas gene that displays retention of intron 5 and encodes a dysfunctional Fas protein in 13 of 22 patients (59%) in both early and advanced CTCL. Impairment of Fas-induced apoptosis resulting from aberrant splicing potentially contributes to the development and progression of CTCL by allowing continued clonal expansion of activated T cells and by reducing susceptibility to antitumor immune responses.
凋亡信号缺陷与原发性皮肤T细胞淋巴瘤（CTCL）的发病机制有关，CTCL是一组源自皮肤归巢T细胞的恶性肿瘤。T细胞凋亡的一个重要介质是Fas受体。我们在22例早期和晚期CTCL患者中的13例（59%）中鉴定出一种新的Fas基因剪接变体，该变体保留了内含子5并编码一种功能失调的Fas蛋白。异常剪接导致的Fas诱导凋亡受损可能通过允许活化T细胞持续克隆扩增以及降低对抗肿瘤免疫反应的敏感性，从而促进CTCL的发生和发展。
