Molecular histogenesis of plasmablastic lymphoma of the oral cavity
Molecular histogenesis of plasmablastic lymphoma of the oral cavity
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DOI：
10.1046/j.1365-2141.2002.03872.x
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发表时间：
2002-12-01
影响因子：
6.5
通讯作者：
Carbone, A
中科院分区：
文献类型：
--
作者：
Gaidano, G;Cerri, M;Carbone, A
口腔浆母细胞淋巴瘤（PBL）是一种与人类免疫缺陷病毒感染相关的侵袭性b细胞淋巴瘤。虽然淋巴瘤表型与b细胞成熟晚期一致，但PBL的分子组织发生尚不清楚。我们研究了口腔PBL （n = 12）的免疫球蛋白可变重链（IgV(H)）和BCL-6基因的突变，这些基因是B细胞在生发中心（GC）转运时获得的，以及BCL-6、um -1和CD138的表达，这些基因是GC B细胞与GC后B细胞的区别。体细胞IgV(H)高突变发生在4/10个PBL中，而6/10个PBL显示种系IgV(H)基因。在携带IgV(H)高突变基因的PBL中，有2例IgV(H)突变模式与抗原刺激一致。BCL-6基因突变仅限于1/12口腔PBL患者。所有口腔PBL病例均表现为BCL-6(-)/MUM-1(+)/CD138（+）表型，与b细胞分化晚期一致。总的来说，这些数据表明，尽管口腔PBL具有共同的表型和明显相似的分化程度，但其特征是组织遗传学异质性。口腔PBL亚群携带GC转运的分子线索，可能起源于与GC后B细胞相对应的B细胞亚群。相反，这些淋巴瘤的另一部分没有体细胞IgV(H)突变，似乎起源于未成熟的B细胞，这些B细胞经历了独立于GC转运的终末分化。
Plasmablastic lymphoma (PBL) of the oral cavity is an aggressive B-cell lymphoma associated with human immunodeficiency virus infection. Although the lymphoma phenotype is consistent with late B-cell maturation, the molecular histogenesis of PBL is unknown. We investigated PBL of the oral cavity (n = 12) for mutations of immunoglobulin variable heavy chain ( IgV(H)) and BCL-6 genes, which are acquired by B cells at the time of germinal centre (GC) transit, and for expression of BCL-6, MUM-1 and CD138, which distinguish GC B cells from post-GC B cells. Somatic IgV(H) hypermutation occurred in 4/10 PBL whereas 6/10 PBL displayed germline IgV(H) genes. Among PBL carrying hypermutated IgV(H) genes, the pattern of IgV(H) mutations was consistent with antigen stimulation in two cases. Mutations of the BCL-6 gene were restricted to 1/12 patients with PBL of the oral cavity. All cases of PBL of the oral cavity displayed the BCL-6(-)/MUM-1(+)/CD138(+) phenotype that is consistent with late stage of B-cell differentiation. Overall, these data indicate that, despite a common phenotype and an apparently similar degree of differentiation, PBL of the oral cavity are characterized by histogenetic heterogeneity. A subset of PBL of the oral cavity carried the molecular clues of GC transit and conceivably originated from a B-cell subset corresponding to post-GC B cells. Conversely, another fraction of these lymphomas were devoid of somatic IgV(H) mutations and appeared to originate from naive B cells that have undergone preterminal differentiation independent of GC transit.