Johansson Patricia, Eckstein Anja, Küppers Ralf
Institute of Cell Biology (Cancer Research), Faculty of Medicine, University of Duisburg-Essen, 45147 Essen, Germany.
Molecular Ophthalmology Group, Department of Ophthalmology, University of Duisburg-Essen, 45147 Essen, Germany.
Cancers (Basel). 2022 Feb 28;14(5):1264. doi: 10.3390/cancers14051264.
This review focuses on the biology of ocular adnexal marginal zone B-cell lymphomas of the mucosa-associated lymphatic tissue (MALT) (OAMZL) subtype. The ocular adnexa includes all structures and tissues within the orbit except for the eye bulb. In the region of the ocular adnexa, MALT lymphomas represent the most common subtype of lymphoma, accounting for around 8% of all non-Hodgkin lymphomas. These lymphomas are often preceded by inflammatory precursor lesions. Either autoantigens or infectious antigens may lead to disease development by functioning as continuous antigenic triggers. This triggering leads to a constitutive activation of the NF-κB signaling pathway. The role of antigenic stimulation in the pathogenesis of OAMZL is supported by the detection of somatic mutations (partially with further intraclonal diversity) in their rearranged immunoglobulin V genes; hence, their derivation from germinal-center-experienced B cells, by a restricted gene usage, and the validation of autoreactivity of the antibodies in selected cases. In the established lymphomas, NF-κB activity is further enforced by mutations in various genes regulating NF-κB activity (e.g., 3, ), as well as recurrent chromosomal translocations affecting NF-κB pathway components in a subset of cases. Further pathogenetic mechanisms include mutations in genes of the NOTCH pathway, and of epigenetic regulators. While gene expression and sequencing studies are available, the role of differential methylation of lymphoma cells, the role of micro-RNAs, and the contribution of the microenvironment remain largely unexplored.
本综述聚焦于黏膜相关淋巴组织（MALT）型眼附属器边缘区B细胞淋巴瘤（OAMZL）的生物学特性。眼附属器包括眼眶内除眼球外的所有结构和组织。在眼附属器区域，MALT淋巴瘤是最常见的淋巴瘤亚型，约占所有非霍奇金淋巴瘤的8%。这些淋巴瘤通常之前存在炎症前驱病变。自身抗原或感染性抗原均可作为持续的抗原触发因素导致疾病发生。这种触发导致NF-κB信号通路的组成性激活。在其重排的免疫球蛋白V基因中检测到体细胞突变（部分伴有进一步的克隆内多样性），以及它们来源于经历生发中心的B细胞、基因使用受限，以及在部分病例中抗体自身反应性的验证，均支持抗原刺激在OAMZL发病机制中的作用。在已确诊的淋巴瘤中，通过调节NF-κB活性的各种基因（如 3， ）的突变，以及在部分病例中影响NF-κB通路成分的复发性染色体易位，NF-κB活性进一步增强。其他发病机制包括NOTCH通路基因和表观遗传调节因子的突变。虽然已有基因表达和测序研究，但淋巴瘤细胞的差异甲基化作用、微小RNA的作用以及微环境的贡献在很大程度上仍未得到探索。
