Ariatti C, Vivenza D, Capello D, Migliazza A, Parvis G, Fassone L, Buonaiuto D, Savinelli F, Rossi D, Saglio G, Gaidano G
Department of Medical Sciences, Amedeo Avogadro University of Eastern Piedmont, Novara, Italy.
Hum Pathol. 2000 Jul;31(7):871-3. doi: 10.1053/hupa.2000.7626.
Common-variable immunodeficiency (CVI) patients develop non-Hodgkin's lymphomas (NHL), mainly B-lineage diffuse large-cell lymphomas (DLCL), with a high relative risk. The molecular pathogenesis of CVI-related NHL (CVI-NHL) is unknown. Here we aimed at providing a detailed molecular characterization of CVI-NHL. Rearrangements of BCL-6 were detected in two thirds of CVI-NHL cases examined. All 3 CVI-NHL also harbored point mutations of the BCL-6 5' noncoding regions, which constitute a marker of B-cell transit through the germinal center (GC). The number and molecular pattern of BCL-6 mutations in CVI-NHL were similar to that detected in DLCL of immunocompetent hosts and in DLCL arising in other immunodeficiency settings. Microsatellite instability occurred in one CVI-NHL devoid of a BCL-6 rearrangement. All CVI-NHL scored negative for genetic lesions of BCL-2, p53, c-MYC, REL as well as for viral infection by EBV and HHV-8. Overall, these data indicate that: similarly to other immunodeficiency-related NHL, involvement of BCL6 occurs frequently also in CVI-NHL; and because BCL-6 mutations are acquired by B cells during GC transit, their occurrence in CVI-NHL suggest that these lymphomas are histogenetically related to GC B cells.
常见变异型免疫缺陷（CVI）患者发生非霍奇金淋巴瘤（NHL）的相对风险较高，主要为B细胞系弥漫大B细胞淋巴瘤（DLCL）。CVI相关NHL（CVI-NHL）的分子发病机制尚不清楚。在此，我们旨在对CVI-NHL进行详细的分子特征分析。在三分之二检测的CVI-NHL病例中检测到BCL-6重排。所有3例CVI-NHL还存在BCL-6 5'非编码区的点突变，这是B细胞通过生发中心（GC）的标志物。CVI-NHL中BCL-6突变的数量和分子模式与免疫功能正常宿主的DLCL以及其他免疫缺陷情况下发生的DLCL中检测到的相似。微卫星不稳定性发生在1例无BCL-6重排的CVI-NHL中。所有CVI-NHL的BCL-2、p53、c-MYC、REL基因损伤以及EBV和HHV-8病毒感染检测均为阴性。总体而言，这些数据表明：与其他免疫缺陷相关的NHL相似，BCL6的参与在CVI-NHL中也很常见；并且由于BCL-6突变是B细胞在GC迁移过程中获得的，它们在CVI-NHL中的出现表明这些淋巴瘤在组织发生学上与GC B细胞相关。
