Gaidano G, Capello D, Gloghini A, Pastore C, Migliazza A, Quattrone S, Savinelli F, Buonaiuto D, Cilia A M, Perin T, Pasqualucci L, Canzonieri V, Saglio G, Dalla-Favera R, Carbone A
Department of Medical Sciences, University of Torino at Novara, Italy.
Leuk Lymphoma. 1998 Sep;31(1-2):39-46. doi: 10.3109/10428199809057583.
AIDS-related non-Hodgkin's lymphomas (AIDS-NHL) are classified into Burkitt's lymphoma, diffuse large cell lymphoma (DLCL), and body cavity based lymphoma. The molecular pathogenesis of AIDS-NHL is complex and involves the genetic alteration of several cancer related genes, including the BCL-6 proto-oncogene. BCL-6 encodes a zinc finger transcription factor which is selectively expressed by germinal center (GC) B-cells, but not by pre-GC or post-GC B-cells. Genetic alterations of BCL-6 occur frequently among B-cell NHL and comprise gross rearrangements as well as small mutations of the 5' noncoding region of the gene. Gross rearrangements of BCL-6 among AIDS-NHL cluster with 20% AIDS-DLCL. Conversely, mutations of the 5' noncoding region of BCL-6 occur at sustained frequency throughout the clinico-pathologic spectrum of AIDS-NHL and represent the most common genetic alteration presently detectable in these lymphomas. The frequency of BCL-6 mutations, as well as their location in the proximity of the BCL-6 regulatory regions, suggest that they may play a pathogenetic role in AIDS-related lymphomagenesis. Beside their pathogenetic implications, the occurrence of BCL-6 mutations among AIDS-NHL bears histogenetic relevance because BCL-6 mutations are regarded as a marker of B-cell transition through the GC. Thus, it is conceivable that a large fraction of AIDS-NHL is histogenetically related to GC or post-GC B-cells. This notion is further confirmed by the observation that AIDS-NHL frequently express the BCL-6 protein, which stains selectively GC B-cells throughout B-cell differentiation.
艾滋病相关非霍奇金淋巴瘤（AIDS-NHL）分为伯基特淋巴瘤、弥漫性大细胞淋巴瘤（DLCL）和体腔淋巴瘤。AIDS-NHL的分子发病机制复杂，涉及多个癌症相关基因的遗传改变，包括BCL-6原癌基因。BCL-6编码一种锌指转录因子，其在生发中心（GC）B细胞中选择性表达，而在前GC或后GC B细胞中不表达。BCL-6的遗传改变在B细胞NHL中频繁发生，包括该基因5'非编码区的大片段重排以及小突变。AIDS-NHL中BCL-6的大片段重排在20%的AIDS-DLCL中聚集。相反，BCL-6 5'非编码区的突变在AIDS-NHL整个临床病理谱中持续出现，是目前这些淋巴瘤中最常见的可检测到的遗传改变。BCL-6突变的频率及其在BCL-6调控区域附近的位置表明，它们可能在艾滋病相关淋巴瘤发生中起致病作用。除了其致病意义外，AIDS-NHL中BCL-6突变的发生具有组织发生学相关性，因为BCL-6突变被视为B细胞通过GC转变的标志物。因此，可以想象，很大一部分AIDS-NHL在组织发生学上与GC或后GC B细胞相关。AIDS-NHL经常表达BCL-6蛋白这一观察结果进一步证实了这一观点，BCL-6蛋白在整个B细胞分化过程中选择性地标记GC B细胞。
