弥漫性大 B 细胞淋巴瘤（DLBCL）治疗抵抗的表观遗传机制。
Epigenetic Mechanisms of Therapy Resistance in Diffuse Large B Cell Lymphoma (DLBCL).
机构信息
Division of Hematology and Medical Oncology, Weill Cornell Medicine, New York, NY, United States.
出版信息
Curr Cancer Drug Targets. 2021;21(4):274-282. doi: 10.2174/1568009620666210106122750.
Abstract
Diffuse large B cell lymphoma (DLBCL) is the most common histological subtype of non-Hodgkin B cell lymphoma (NHL), and manifests highly heterogeneous genetic/phenotypic characteristics as well as variable responses to conventional immunochemotherapy. Genetic profiling of DLBCL patients has revealed highly recurrent mutations of epigenetic regulator genes such as CREBBP, KMT2D, EZH2 and TET2. These mutations drive malignant transformation through aberrant epigenetic programming of B-cells and may influence clinical outcomes. These and other chromatin modifier genes also play critical roles in normal B-cells, as they undergo the various phenotypic transitions characteristic of the humoral immune response. Many of these functions have to do with impairing immune surveillance and may critically mediate resistance to immunotherapies. In this review, we describe how epigenetic dysfunction induces lymphomagenesis and discuss ways of implementing precision epigenetic therapies to reverse these immune resistant phenotypes.
摘要
弥漫性大 B 细胞淋巴瘤（DLBCL）是非霍奇金 B 细胞淋巴瘤（NHL）中最常见的组织学亚型，表现出高度异质的遗传/表型特征以及对常规免疫化学疗法的不同反应。对 DLBCL 患者的基因谱分析显示，表观遗传调节基因如 CREBBP、KMT2D、EZH2 和 TET2 经常发生突变。这些突变通过 B 细胞的异常表观遗传编程驱动恶性转化，并可能影响临床结局。这些和其他染色质修饰基因在正常 B 细胞中也起着关键作用，因为它们经历了体液免疫反应的各种表型转变。其中许多功能与削弱免疫监视有关，并可能在很大程度上介导对免疫疗法的耐药性。在这篇综述中，我们描述了表观遗传功能障碍如何诱导淋巴瘤的发生，并讨论了实施精确的表观遗传治疗来逆转这些免疫抵抗表型的方法。
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本文引用的文献
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