Lymphoma Translational Group, Josep Carreras Leukaemia Research Institute (IJC), 08916 Badalona, Spain.
Department of Biochemistry and Molecular Biology, Autonomous University of Barcelona, 08014 Barcelona, Spain.
Int J Mol Sci. 2021 Dec 27;23(1):253. doi: 10.3390/ijms23010253.
In a wide range of lymphoid neoplasms, the process of malignant transformation is associated with somatic mutations in B cells that affect the epigenetic machinery. Consequential alterations in histone modifications contribute to disease-specific changes in the transcriptional program. Affected genes commonly play important roles in cell cycle regulation, apoptosis-inducing signal transduction, and DNA damage response, thus facilitating the emergence of malignant traits that impair immune surveillance and favor the emergence of different B-cell lymphoma subtypes. In the last two decades, the field has made a major effort to develop therapies that target these epigenetic alterations. In this review, we discuss which epigenetic alterations occur in B-cell non-Hodgkin lymphoma. Furthermore, we aim to present in a close to comprehensive manner the current state-of-the-art in the preclinical and clinical development of epigenetic drugs. We focus on therapeutic strategies interfering with histone methylation and acetylation as these are most advanced in being deployed from the bench-to-bedside and have the greatest potential to improve the prognosis of lymphoma patients.
在广泛的淋巴肿瘤中，恶性转化过程与影响表观遗传机制的 B 细胞体细胞突变有关。组蛋白修饰的后续改变导致转录程序发生疾病特异性变化。受影响的基因通常在细胞周期调控、凋亡诱导信号转导和 DNA 损伤反应中发挥重要作用，从而促进恶性特征的出现，损害免疫监视并有利于不同 B 细胞淋巴瘤亚型的出现。在过去的二十年中，该领域做出了重大努力来开发针对这些表观遗传改变的治疗方法。在这篇综述中，我们讨论了 B 细胞非霍奇金淋巴瘤中发生了哪些表观遗传改变。此外，我们旨在以近乎全面的方式介绍表观遗传药物在临床前和临床开发中的最新进展。我们专注于干扰组蛋白甲基化和乙酰化的治疗策略，因为这些策略在从实验室到临床的应用中最为先进，并且具有最大的潜力来改善淋巴瘤患者的预后。
