Xerri L, Parc P, Brousset P, Schlaifer D, Hassoun J, Reed J C, Krajewski S, Birnbaum D
Departement de Pathologie, Institut Paoli-Calmettes, Marseille, France.
Br J Haematol. 1996 Mar;92(4):900-6. doi: 10.1046/j.1365-2141.1996.423958.x.
Bcl-x is a member of the bcl-2 family of proteins which are characterized by their ability to modulate apoptosis. Alternative splicing results in two distinct bcl-x mRNAs encoding a long isoform, bcl-xL, which acts as a bcl-2 agonist; and a short isoform, bcl-xS, which inhibits bcl-2 effects. The aim of the study was to determine whether bcl-x is expressed in lymphoma tissues and to characterize the respective production of bcl-xs and bcl-xL. We investigated the expression of bcl-x mRNA in a series of 50 non-Hodgkin's lymphomas (NHL) and Hodgkin's disease (HD) cases using a RT-PCR method in order to amplify both transcripts simultaneously, and to estimate their relative abundance. The rearrangements of the bcl-2 gene were analysed by RT-PCR expression of the hybrid bcl-2-lgH mRNA. In addition, 20 PCR-positive NHL cases and three HD cases were analysed by immunohistochemistry using bcl-x polyclonal antisera. RT-PCR showed bcl-x expression in 43/45 NHLs and 5/5 HD cases. The bcl-xL transcript was predominant in all positive cases and was associated with variable amounts of bcl-xS. There was no significant correlation between the profile of bcl-xL/bcl-xS expression and the histological and immunological subtyping. Bcl-x immunodetection was positive in the neoplastic cell component in all analysed cases, but the degree of staining was highly variable between cases. Expression of the hybrid bcl-2-IgH gene was detected by RT-PCR in five cases of follicular NHL and in one case of HD, but this group of tumours did not display a particular profile of bcl-xL/bcl-xS expression. We conclude that bcl-x is commonly expressed by malignant cells in various types of malignant lymphomas, with a predominance of the bcl-xL transcript. Since the corresponding bcl-xL isoform can block the cell death machinery and potentialize bcl-2 effects, it may be involved in some pathways of lymphomagenesis.
Bcl-x是bcl-2蛋白家族的成员之一，其特点是能够调节细胞凋亡。选择性剪接产生两种不同的bcl-x mRNA，分别编码长异构体bcl-xL，它作为bcl-2激动剂发挥作用；以及短异构体bcl-xS，它抑制bcl-2的作用。本研究的目的是确定bcl-x是否在淋巴瘤组织中表达，并对bcl-xS和bcl-xL的各自产生情况进行表征。我们使用逆转录聚合酶链反应（RT-PCR）方法，对50例非霍奇金淋巴瘤（NHL）和霍奇金病（HD）病例进行了研究，以同时扩增两种转录本，并估计它们的相对丰度。通过杂交bcl-2-lgH mRNA的RT-PCR表达分析bcl-2基因的重排情况。此外，使用bcl-x多克隆抗血清通过免疫组织化学方法对20例PCR阳性的NHL病例和3例HD病例进行了分析。RT-PCR显示，在45例NHL中的43例以及5例HD病例中存在bcl-x表达。在所有阳性病例中，bcl-xL转录本占主导地位，并与不同量的bcl-xS相关。bcl-xL/bcl-xS表达谱与组织学和免疫学亚型之间无显著相关性。在所有分析病例的肿瘤细胞成分中，bcl-x免疫检测均为阳性，但不同病例之间的染色程度差异很大。通过RT-PCR在5例滤泡性NHL病例和1例HD病例中检测到杂交bcl-2-IgH基因的表达，但这组肿瘤并未表现出特定的bcl-xL/bcl-xS表达谱。我们得出结论，bcl-x在各种类型的恶性淋巴瘤中通常由恶性细胞表达，其中bcl-xL转录本占主导。由于相应的bcl-xL异构体可以阻断细胞死亡机制并增强bcl-2的作用，它可能参与了淋巴瘤发生的某些途径。
