Department of Microbiology and Immunology, Louisiana State University Health Sciences Center, Shreveport, LA, 71130, USA.
Commun Biol. 2020 Nov 12;3(1):667. doi: 10.1038/s42003-020-01391-5.
Keeping a balance between DNA methylation and demethylation balance is central for mammalian development and cell function, particularly in the hematopoietic system. In various mammalian cells, Tet methylcytosine dioxygenase 2 (Tet2) catalyzes oxygen transfer to a methyl group of 5-methylcytosine (5mC), yielding 5-hydroxymethylcytocine (5hmC). Tet2 mutations drive tumorigenesis in several blood cancers as well as in solid cancers. Here I discuss recent studies that elucidate mechanisms and biological consequences of Tet2 dysregulation in blood cancers. I focus on recent findings concerning Tet2 involvement in lymphoid and myeloid cell development and its functional roles, which may be associated with tumorigenesis. I also discuss how Tet2 activities are modulated by microRNAs, metabolites, and other interactors, including vitamin C and 2-hydroxyglutarate (2-HG), and review the clinical relevance and potential therapeutic applications of Tet2 targeting. Finally, I propose key unanswered hypotheses regarding Tet2 in the cancer-immunity cycle.
维持 DNA 甲基化和去甲基化平衡对于哺乳动物的发育和细胞功能至关重要，特别是在造血系统中。在各种哺乳动物细胞中，Tet 甲基胞嘧啶双加氧酶 2（Tet2）催化氧转移到 5-甲基胞嘧啶（5mC）的甲基上，生成 5-羟甲基胞嘧啶（5hmC）。Tet2 突变可导致多种血液癌以及实体癌的肿瘤发生。在这里，我将讨论最近的研究，这些研究阐明了 Tet2 在血液癌中失调的机制和生物学后果。我将重点介绍最近发现的关于 Tet2 参与淋巴样和髓样细胞发育及其功能作用的研究，这些研究可能与肿瘤发生有关。我还讨论了 Tet2 的活性如何被 microRNAs、代谢物和其他相互作用因子（包括维生素 C 和 2-羟戊二酸（2-HG））调节，并回顾了 Tet2 靶向的临床相关性和潜在治疗应用。最后，我提出了关于 Tet2 在癌症-免疫循环中的关键未解答假说。
