表观遗传学在淋巴系统肿瘤研究中的新进展

表观遗传学是研究不涉及DNA序列改变的基因表达和调控的可遗传修饰,即探索从基因演绎为表型的过程和机制的一门新兴学科。近年来诸多证据显示,表观遗传学改变在淋巴系统肿瘤发生发展过程中起重要作用。例如,近期多个实验室的资料显示,参与许多重要分子信号通路的基因在急性淋巴细胞白血病中是表观抑制的;一组甲基化标志可被用作慢性淋巴细胞白血病患者额外的危险分层因素;基于表观遗传学甲基化谱研究中间性(灰区)B细胞淋巴瘤类别划分模型;多发性骨髓瘤中mciroRNA介导的表观遗传学沉默与P53功能联系密切;表观遗传修饰治疗赋予免疫治疗更广的内涵,其可能是极富潜力的免疫治疗策略之一。本文就淋巴系统肿瘤中表观遗传学改变的最新研究进展及通过干预表观遗传修饰治疗的相关研究和应用前景做一综述。

New advances of epigenetic study in tumors of lymphatic system---review

Epigenetics is aimed to study the heritable changes in gene expression patterns independent of alterations in genomic DNA sequence structure, and the mechanisms of translation from genotype to phenotype. In recent years, compelling evidence gathered supports a role of epigenetic alterations in the pathogenesis of lymphatic system tumors. For example, recent data from multiple laboratories indicate that several hundred genes, involving dozens of critical molecular pathways, are epigenetically suppressed in acute lymphocytic leukemia; a panel of methylation markers can be used for additional risk stratification of chronic lymphocytic leukemia patients; based on the epigenetic profiles, the class prediction models in gray zone lymphoma can be established; the epigenetic silencing of microRNAs in multiple myeloma generally appears to have intact P53 function; epigenetic therapies have broader implication and high potential for the development of immunotherapeutic strategies and so on. In this review, the latest advances of epigenetic study and the prospect of epigenetic therapy for tumors in lymphatic system are summarized.