Rossi Davide, Gaidano Gianluca
Hematology Unit, Division of Internal Medicine, Department of Medical Sciences and IRCAD, Amedeo Avogadro University of Eastern Piedmont, Via Solaroli 17, I-28100, Novara, Italy.
Hematology. 2002 Aug;7(4):239-52. doi: 10.1080/1024533021000024058.
Diffuse large B-cell lymphoma (DLBCL) accounts for approximately 40% of all B-cell non-Hodgkin lymphomas of the Western world. According to the "WHO classification of tumours of the haematopoietic and lymphoid tissues", the term DLBCL is likely to include more than one disease entity, as suggested by the marked variability of the clinical presentation and response to treatment of this disease. Such heterogeneity may reflect the occurrence of distinct molecular subtypes of DLBCL as well as differences in the host's immune function. In immunocompetent hosts, approximately 50% DLBCL carry one of two primary molecular lesions defining two distinct genotypic subgroups, characterized by activation of either the BCL-6 or the BCL-2 proto-oncogene. Conversely, the remaining DLBCL of immunocompetent hosts display one of several molecular lesions, each associated with a small subset of cases and including activation of the proto-oncogenes REL, MUC-1, BCL-8 and c-MYC. The molecular pathogenesis of immunodeficiency-associated DLBCL differs substantially from that of DLBCL in immunocompetent hosts. In fact, EBV infection is present in a large fraction of immunodeficiency-associated DLBCL, whereas it is consistently negative in DLBCL of immunocompetent hosts, probably reflecting the critical role of disruption of the immune system in this disease. Finally, the application of DNA microarray technology to DLBCL has led to the distinction of two disease variants: a germinal center like DLBCL and an activated peripheral B-cell like DLBCL. Overall the molecular features of DLBCL may identify prognostic categories of the disease and may represent a powerful tool for therapeutic stratification.
弥漫性大B细胞淋巴瘤（DLBCL）约占西方世界所有B细胞非霍奇金淋巴瘤的40%。根据“世界卫生组织造血与淋巴组织肿瘤分类”，DLBCL这一术语可能包含不止一种疾病实体，因为该疾病临床表现和对治疗反应的显著变异性表明了这一点。这种异质性可能反映了DLBCL不同分子亚型的出现以及宿主免疫功能的差异。在免疫功能正常的宿主中，约50%的DLBCL存在两种主要分子病变之一，这两种病变定义了两个不同的基因型亚组，其特征分别为BCL-6或BCL-2原癌基因的激活。相反，免疫功能正常宿主中其余的DLBCL表现出几种分子病变之一，每种病变与一小部分病例相关，包括原癌基因REL、MUC-1、BCL-8和c-MYC的激活。免疫缺陷相关DLBCL的分子发病机制与免疫功能正常宿主中的DLBCL有很大不同。事实上，很大一部分免疫缺陷相关DLBCL存在EBV感染，而在免疫功能正常宿主的DLBCL中则始终为阴性，这可能反映了免疫系统破坏在该疾病中的关键作用。最后，DNA微阵列技术应用于DLBCL已导致区分出两种疾病变体：生发中心样DLBCL和活化外周B细胞样DLBCL。总体而言，DLBCL的分子特征可能确定该疾病的预后类别，并可能成为治疗分层的有力工具。
