Institute for Cancer Genetics, Columbia University, New York, NY, United States.
Department of Biological Sciences & Geology, Queensborough Community College (City University of New York), Bayside, NY, United States.
Front Immunol. 2021 Aug 12;12:710711. doi: 10.3389/fimmu.2021.710711. eCollection 2021.
Over the last decades, the revolution in DNA sequencing has changed the way we understand the genetics and biology of B-cell lymphomas by uncovering a large number of recurrently mutated genes, whose aberrant function is likely to play an important role in the initiation and/or maintenance of these cancers. Dissecting how the involved genes contribute to the physiology and pathology of germinal center (GC) B cells -the origin of most B-cell lymphomas- will be key to advance our ability to diagnose and treat these patients. Genetically engineered mouse models (GEMM) that faithfully recapitulate lymphoma-associated genetic alterations offer a valuable platform to investigate the pathogenic roles of candidate oncogenes and tumor suppressors , and to pre-clinically develop new therapeutic principles in the context of an intact tumor immune microenvironment. In this review, we provide a summary of state-of-the art GEMMs obtained by accurately modelling the most common genetic alterations found in human GC B cell malignancies, with a focus on Burkitt lymphoma, follicular lymphoma, and diffuse large B-cell lymphoma, and we discuss how lessons learned from these models can help guide the design of novel therapeutic approaches for this disease.
在过去的几十年中，DNA 测序技术的革命通过揭示大量经常发生突变的基因，改变了我们对 B 细胞淋巴瘤遗传学和生物学的理解，这些基因的异常功能可能在这些癌症的发生和/或维持中发挥重要作用。解析涉及的基因如何促进生发中心 (GC) B 细胞——大多数 B 细胞淋巴瘤的起源——的生理学和病理学，将是提高我们诊断和治疗这些患者能力的关键。准确模拟人类 GC B 细胞恶性肿瘤中常见遗传改变的基因工程小鼠模型 (GEMM) 为研究候选癌基因和肿瘤抑制基因的致病作用提供了宝贵的平台，并在完整的肿瘤免疫微环境背景下，为临床前开发新的治疗原则提供了可能。在这篇综述中，我们总结了通过精确模拟人类 GC B 细胞恶性肿瘤中最常见遗传改变而获得的最先进的 GEMM，重点介绍了 Burkitt 淋巴瘤、滤泡性淋巴瘤和弥漫性大 B 细胞淋巴瘤，并讨论了从这些模型中获得的经验教训如何有助于指导针对这种疾病的新型治疗方法的设计。
