Pelicci P G, Knowles D M, Arlin Z A, Wieczorek R, Luciw P, Dina D, Basilico C, Dalla-Favera R
J Exp Med. 1986 Dec 1;164(6):2049-60. doi: 10.1084/jem.164.6.2049.
AIDS (acquired immune deficiency syndrome) and ARC (AIDS-related complex) are associated with a spectrum of lymphoproliferative disorders ranging from lymphadenopathy syndrome (LAS), an apparently benign polyclonal lymphoid hyperplasia, to B cell non-Hodgkin's lymphoma (B-NHL), i.e., malignant, presumably monoclonal B cell proliferations. To gain insight into the process of lymphomagenesis in AIDS and to investigate a possible pathogenetic relationship between LAS and NHL, we investigated the clonality of the B or T lymphoid populations by Ig or T beta gene rearrangement analysis, the presence of rearrangements involving the c-myc oncogene locus, and the presence of human immunodeficiency virus (HIV) sequences in both LAS and B-NHL biopsies. Our data indicate that multiple clonal B cell expansions are present in a significant percentage of LAS (approximately 20%) and B-NHL (60%) biopsies. c-myc rearrangements/translocations are detectable in 9 of our 10 NHLs, but not in any of the LAS cases. However, only one of the B cell clones, identified by Ig gene rearrangements carries a c-myc gene rearrangement, suggesting that only one clone carries the genetic abnormality associated with malignant B cell lymphoma. Furthermore, the frequency of detection of c-myc rearrangements in AIDS-associated NHLs of both Burkitt and non-Burkitt type suggest that the biological alterations present in AIDS favor the development of lymphomas carrying activated c-myc oncogenes. Finally, our data show that HIV DNA sequences are not detectable in LAS nor in NHL B cell clones, suggesting that HIV does not play a direct role in NHL development. Taken together, these observations suggest a model of multistep lymphomagenesis in AIDS in which LAS would represent a predisposing condition to NHL. Immunosuppression and EBV infection present in LAS can favor the expansion of B cell clones, which in turn may increase the probability of occurrence of c-myc rearrangements leading to malignant transformation.
获得性免疫缺陷综合征（AIDS）和艾滋病相关综合征（ARC）与一系列淋巴增殖性疾病相关，范围从淋巴结病综合征（LAS），一种明显良性的多克隆淋巴样增生，到B细胞非霍奇金淋巴瘤（B-NHL），即恶性的、推测为单克隆的B细胞增殖。为了深入了解AIDS中淋巴瘤发生的过程，并研究LAS和NHL之间可能的致病关系，我们通过Ig或Tβ基因重排分析研究了B或T淋巴细胞群体的克隆性、涉及c-myc癌基因位点的重排情况，以及LAS和B-NHL活检组织中人类免疫缺陷病毒（HIV）序列的存在情况。我们的数据表明，在相当比例的LAS（约20%）和B-NHL（60%）活检组织中存在多个克隆性B细胞扩增。在我们的10例NHL中有9例可检测到c-myc重排/易位，但LAS病例中均未检测到。然而，通过Ig基因重排鉴定的B细胞克隆中只有一个携带c-myc基因重排，这表明只有一个克隆携带与恶性B细胞淋巴瘤相关的基因异常。此外，在伯基特型和非伯基特型的AIDS相关NHL中检测到c-myc重排的频率表明，AIDS中存在的生物学改变有利于携带激活的c-myc癌基因的淋巴瘤的发展。最后，我们的数据表明，在LAS或NHL B细胞克隆中均未检测到HIV DNA序列，这表明HIV在NHL发展中不发挥直接作用。综上所述，这些观察结果提示了AIDS中多步骤淋巴瘤发生的模型，其中LAS可能是NHL的易感状态。LAS中存在的免疫抑制和EBV感染可促进B细胞克隆的扩增，这反过来可能增加发生c-myc重排导致恶性转化的概率。
