Zhang Q, Siebert R, Yan M, Hinzmann B, Cui X, Xue L, Rakestraw K M, Naeve C W, Beckmann G, Weisenburger D D, Sanger W G, Nowotny H, Vesely M, Callet-Bauchu E, Salles G, Dixit V M, Rosenthal A, Schlegelberger B, Morris S W
Department of Pathology and Laboratory Medicine, St. Jude Children's Research Hospital, Memphis, Tennessee 38105, USA.
Nat Genet. 1999 May;22(1):63-8. doi: 10.1038/8767.
Mucosa-associated lymphoid tissue (MALT) lymphomas most frequently involve the gastrointestinal tract and are the most common subset of extranodal non-Hodgkin lymphoma (NHL). Here we describe overexpression of BCL10, a novel apoptotic signalling gene that encodes an amino-terminal caspase recruitment domain (CARD), in MALT lymphomas due to the recurrent t(1;14)(p22;q32). BCL10 cDNAs from t(1;14)-positive MALT tumours contained a variety of mutations, most resulting in truncations either in or carboxy terminal to the CARD. Wild-type BCL10 activated NF-kappaB but induced apoptosis of MCF7 and 293 cells. CARD-truncation mutants were unable to induce cell death or activate NF-kappaB, whereas mutants with C-terminal truncations retained NF-kappaB activation but did not induce apoptosis. Mutant BCL10 overexpression might have a twofold lymphomagenic effect: loss of BCL10 pro-apoptosis may confer a survival advantage to MALT B-cells, and constitutive NF-kappaB activation may provide both anti-apoptotic and proliferative signals mediated via its transcriptional targets.
黏膜相关淋巴组织（MALT）淋巴瘤最常累及胃肠道，是结外非霍奇金淋巴瘤（NHL）最常见的亚型。在此，我们描述了由于复发性t(1;14)(p22;q32)导致的MALT淋巴瘤中BCL10的过表达，BCL10是一种新的凋亡信号基因，编码一个氨基末端半胱天冬酶募集结构域（CARD）。来自t(1;14)阳性MALT肿瘤的BCL10 cDNA包含多种突变，大多数导致CARD内或其羧基末端的截短。野生型BCL10激活NF-κB，但诱导MCF7和293细胞凋亡。CARD截短突变体无法诱导细胞死亡或激活NF-κB，而羧基末端截短的突变体保留NF-κB激活但不诱导凋亡。突变型BCL10的过表达可能具有双重致淋巴瘤作用：BCL10促凋亡功能的丧失可能赋予MALT B细胞生存优势，而组成型NF-κB激活可能通过其转录靶点提供抗凋亡和增殖信号。
