Department of Oncology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou City, 450052, Henan Province, China.
Academy of Medical Sciences of Zhengzhou University, Zhengzhou City, 450052, Henan Province, China.
Clin Epigenetics. 2020 Nov 7;12(1):169. doi: 10.1186/s13148-020-00962-x.
Peripheral T-cell lymphoma (PTCL) is a rare and heterogeneous group of clinically aggressive diseases associated with poor prognosis. Except for ALK + anaplastic large-cell lymphoma (ALCL), most peripheral T-cell lymphomas are highly malignant and have an aggressive disease course and poor clinical outcomes, with a poor remission rate and frequent relapse after first-line treatment. Aberrant epigenetic alterations play an important role in the pathogenesis and development of specific types of peripheral T-cell lymphoma, including the regulation of the expression of genes and signal transduction. The most common epigenetic alterations are DNA methylation and histone modification. Histone modification alters the level of gene expression by regulating the acetylation status of lysine residues on the promoter surrounding histones, often leading to the silencing of tumour suppressor genes or the overexpression of proto-oncogenes in lymphoma. DNA methylation refers to CpG islands, generally leading to tumour suppressor gene transcriptional silencing. Genetic studies have also shown that some recurrent mutations in genes involved in the epigenetic machinery, including TET2, IDH2-R172, DNMT3A, RHOA, CD28, IDH2, TET2, MLL2, KMT2A, KDM6A, CREBBP, and EP300, have been observed in cases of PTCL. The aberrant expression of miRNAs has also gradually become a diagnostic biomarker. These provide a reasonable molecular mechanism for epigenetic modifying drugs in the treatment of PTCL. As epigenetic drugs implicated in lymphoma have been continually reported in recent years, many new ideas for the diagnosis, treatment, and prognosis of PTCL originate from epigenetics in recent years. Novel epigenetic-targeted drugs have shown good tolerance and therapeutic effects in the treatment of peripheral T-cell lymphoma as monotherapy or combination therapy. NCCN Clinical Practice Guidelines also recommended epigenetic drugs for PTCL subtypes as second-line therapy. Epigenetic mechanisms provide new directions and therapeutic strategies for the research and treatment of peripheral T-cell lymphoma. Therefore, this paper mainly reviews the epigenetic changes in the pathogenesis of peripheral T-cell lymphoma and the advancement of epigenetic-targeted drugs in the treatment of peripheral T-cell lymphoma (PTCL).
外周 T 细胞淋巴瘤（PTCL）是一组罕见且异质性的侵袭性临床疾病，预后不良。除 ALK+间变性大细胞淋巴瘤（ALCL）外，大多数外周 T 细胞淋巴瘤恶性程度高，疾病进展迅速，临床结局差，缓解率低，一线治疗后频繁复发。异常的表观遗传改变在外周 T 细胞淋巴瘤的发病机制和发展中起着重要作用，包括调节基因表达和信号转导。最常见的表观遗传改变是 DNA 甲基化和组蛋白修饰。组蛋白修饰通过调节组蛋白周围启动子上赖氨酸残基的乙酰化状态来改变基因表达水平，常导致肿瘤抑制基因失活或原癌基因在淋巴瘤中过度表达。DNA 甲基化是指 CpG 岛，通常导致肿瘤抑制基因转录沉默。遗传学研究还表明，PTCL 中存在一些表观遗传机制相关基因的反复突变，包括 TET2、IDH2-R172、DNMT3A、RHOA、CD28、IDH2、TET2、MLL2、KMT2A、KDM6A、CREBBP 和 EP300。miRNA 的异常表达也逐渐成为诊断生物标志物。这些为 PTCL 治疗中表观遗传修饰药物提供了合理的分子机制。近年来，与淋巴瘤相关的表观遗传药物不断被报道，近年来，表观遗传学为 PTCL 的诊断、治疗和预后提供了许多新的思路。新型表观遗传靶向药物作为单一药物或联合治疗在治疗外周 T 细胞淋巴瘤方面显示出良好的耐受性和治疗效果。NCCN 临床实践指南也推荐将表观遗传药物作为 PTCL 亚型的二线治疗。表观遗传机制为外周 T 细胞淋巴瘤的研究和治疗提供了新的方向和治疗策略。因此，本文主要综述了外周 T 细胞淋巴瘤发病机制中的表观遗传改变及表观遗传靶向药物在治疗外周 T 细胞淋巴瘤中的进展。
