Manu Gloria Pokuaa, Odabashian Mariette, Krysov Sergey
Barts Cancer Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London EC1M 6BQ, UK.
West African Centre for Cell Biology of Infectious Pathogens, Department of Biochemistry Cell and Molecular Biology, University of Ghana, Legon, Accra P.O. Box LG 54, Ghana.
Cancers (Basel). 2025 Apr 4;17(7):1219. doi: 10.3390/cancers17071219.
Follicular lymphoma (FL) is a heterogeneous and incurable disease. One of the hallmark features of FL cells is the introduction of N-glycosylation (N-gly) amino acid sequence motifs into the immunoglobulin variable (IgV) region through ongoing somatic hypermutation (SHM) in the early stages of lymphoma development. These N-gly motifs, containing oligomannoses, are rarely found in healthy B cells but evidently play a crucial role in the clonal evolution and survival of FL cells in the hostile environment of germinal centers. The random nature of the ongoing SHM in FL occasionally results in the loss of productive immunoglobulin (Ig) genes or the elimination of N-gly motifs in productive genes. Such events typically lead to clonal deletion, as demonstrated by the longitudinal analysis of FL samples. However, rare N-gly-negative subclones demonstrate prolonged survival with evidence of ongoing SHM, giving rise to new N-gly-negative subclones before eventual deletion. This observation suggests the presence of specific mechanisms supporting their survival and proliferation. This perspective examines the current literature and explores whether a detailed transcriptomic and functional comparison of FL subclones characterized by different N-gly statuses, with a particular focus on N-gly-negative subclones, will lead to a comprehensive understanding of both N-gly-dependent and independent pro-survival and proliferative transcriptional signatures. Specifically, it aims to deepen our understanding of FL pathobiology and identify novel therapeutic targets for better disease management.
滤泡性淋巴瘤（FL）是一种异质性且无法治愈的疾病。FL细胞的标志性特征之一是在淋巴瘤发展的早期阶段，通过持续的体细胞超突变（SHM）将N-糖基化（N-gly）氨基酸序列基序引入免疫球蛋白可变区（IgV）。这些含有低聚甘露糖的N-gly基序在健康B细胞中很少见，但显然在生发中心的恶劣环境中对FL细胞的克隆进化和存活起着关键作用。FL中持续的SHM的随机性偶尔会导致有功能的免疫球蛋白（Ig）基因丢失或有功能基因中的N-gly基序消除。如对FL样本的纵向分析所示，此类事件通常会导致克隆缺失。然而，罕见的N-糖基化阴性亚克隆显示出延长的生存期，并有持续SHM的证据，在最终缺失之前会产生新的N-糖基化阴性亚克隆。这一观察结果表明存在支持它们存活和增殖的特定机制。本观点审视了当前文献，并探讨对具有不同N-糖基化状态特征的FL亚克隆，特别是聚焦于N-糖基化阴性亚克隆进行详细的转录组学和功能比较，是否会带来对N-糖基化依赖性和非依赖性促存活及增殖转录特征的全面理解。具体而言，其旨在加深我们对FL病理生物学的理解，并确定新的治疗靶点以更好地管理疾病。
