Department of Pathology, New York University School of Medicine, New York, NY 10016, USA; Laura and Isaac Perlmutter Cancer Center, New York University School of Medicine, New York, NY 10016, USA.
Department of Pathology, New York University School of Medicine, New York, NY 10016, USA; Laura and Isaac Perlmutter Cancer Center, New York University School of Medicine, New York, NY 10016, USA.
Trends Immunol. 2019 Sep;40(9):809-824. doi: 10.1016/j.it.2019.07.003. Epub 2019 Aug 15.
Epigenetic dysregulation plays a profound role in the pathogenesis of hematological malignancies, which is often the result of somatic mutations of chromatin regulators. Previously, these mutations were largely considered to alter gene expression in two dimensions, by activating or repressing chromatin states; however, research in the last decade has highlighted the increasing impact of the 3D organization of the genome in gene regulation and disease pathogenesis. Here, we summarize the current principles of 3D chromatin organization, how the integrity of the 3D genome governs immune cell development and malignant transformation, as well as how underlying (epi-)genetic drivers of 3D chromatin alterations might act as potential novel therapeutic targets for hematological malignancies.
表观遗传失调在血液系统恶性肿瘤的发病机制中起着深远的作用,这通常是染色质调节因子的体细胞突变的结果。以前,这些突变主要被认为通过激活或抑制染色质状态在二维空间上改变基因表达;然而,过去十年的研究强调了基因组三维结构在基因调控和疾病发病机制中的影响日益增加。在这里,我们总结了三维染色质组织的当前原理,三维基因组的完整性如何控制免疫细胞的发育和恶性转化,以及三维染色质改变的潜在(表观)遗传驱动因素如何作为血液系统恶性肿瘤的潜在新治疗靶点。