DNA甲基化是指以共价结合方式获得一个甲基（CH3）基团的过程，其是在DNA序列特定碱基的DNMT催化下作为CH3供体的S-腺苷甲硫氨酸（SAM）的化学修饰过程。 在此过程中， 胞嘧啶 （C）是甲基化最常见碱基，且C位点甲基化主要发生在CpG序列上。 在哺乳动物中，部分CpG二核苷酸分散在基因组中，而另一些则出现在CpG岛的密集簇中。 CpG岛通常是未甲基化的，常位于调控转录起始和抑制的基因启动子区域中。 增强子或启动子中CpG位点高甲基化通常导致转 …

2020年7月7日 · DNA methyltransferases (DNMTs) by regulating DNA methylation play crucial roles in the progression of hematologic malignancies, especially for acute myeloid leukemia (AML). Accumulating investigations have identified the high incidence of DNMT3A mutation in AML, and it is correlated with poor prognosis.

2019年5月8日 · DNMTs are frequently implicated in the pathogenesis and aggressiveness of acute myeloid leukaemia (AML) patients. In this review, we describe and discuss the oncogenic roles of DNMT1, DNMT3A, and DNMT3B in AML.

2016年10月10日 · We introduce a mechanism-based strategy to enhance PARPi efficacy based on DNA damage-related binding between DNA methyltransferases (DNMTs) and PARP1. In acute myeloid leukemia (AML) and breast cancer cells, DNMT inhibitors (DNMTis) alone covalently bind DNMTs into DNA and increase PARP1 tightly bound into chromatin.

2024年12月12日 · Here, we demonstrate that AMLs carrying DNMT3A and Nucleophosmin (NPM1) mutations exhibit a specific epigenetic vulnerability toward a complex formed by DNMTs and G9a, a specific histone H3 Lysine 9 Methyltransferase (H3K9-HMT).

2024年7月30日 · This article provides a comprehensive summary and the latest insights into the structure and function of DNMT3A, examines the impact of DNMT3A mutations on the progression and prognosis of AML, and explores potential therapeutic approaches for AML patients harboring DNMT3A mutations.

2023年11月11日 · This study aimed to investigate the biological function and mechanism of SOCS3 methylation mediated by DNMTs in the development of AML. Methods: Bone marrow samples were collected from 70 AML patients and 20 healthy volunteers. The expression and methylation status of each gene were detected by RT-qPCR, western blot …

2012年11月16日 · In order to investigate the expression pattern of DNA methyltransferases (DNMTs) in AML patients, we established a tissue microarray (TMA) on bone marrow biopsies of 127 patients diagnosed with AML, who received intensive treatment in our department between 1999 and 2008 and with available bone marrow histology specimens.

2011年3月11日 · Our results suggest that DNMT3a mutations may precede the development of AML. MDS is a heterogenous group of clonal bone marrow disorders characterized by ineffective hematopoiesis, cytopenias and increased risk of AML. On a cellular level, there is an increased rate of proliferation accompanied by an increase in apoptosis.

摘要: 研究DNA甲基转移酶（DNA methyltransferase，DNMT）基因在骨髓增生异常综合征（MDS）患者中的表达及其与抑癌基因p15INK4B甲基化状态的相关性，并进一步探讨其与临床预后的关系。 方法：采用SYBR Green I实时定量逆转录聚合酶链反应（Real-time RT-PCR）方法对48例初治MDS患者和20例正常人骨髓进行DNMT1、DNMT3A、DNMT3B mRNA水平检测；采用甲基化特异性PCR（MSP-PCR）方法检测48例初治MDS患者和20例正常人p15INK4B基因的甲 …

In acute myeloid leukemia (AML) and chronic myeloid leukemia (CML), The three DNMTs are overexpressed. DNMT1 and DNMT3A have been described as affected in liver cancer and pituitary cancer, while DNMT1 and DNMT3B are overexpressed in breast cancer, colon cancer, and lung cancer; DNMT3B is deregulated in colon cancer and prostate cancer, and ...

2011年3月18日 · DNMT3A mutations have recently been reported in patients with de novo acute myeloid leukemia (AML), providing a rationale for examining the status of DNMT3A in MDS samples. In this study, we...

2025年2月5日 · DNMTs facilitate the methylation of cytosines within CpG dinucleotides located in gene promoter regions. They achieve this by transferring methyl groups from the methyl donor, SAM, forming 5mC and SAH. The hypermethylation …

2023年12月1日 · In human acute myeloid leukemia (AML), the lncRNA HOTAIR recruits DNMT3B, resulting in hypermethylation of the HOXA5 promoter (Wang et al., 2019). Moreover, lncRNA ZFAS1 can recruit DNMT3B to the promotor of …

Aberrant DNA methylation at the 5-position of cytosine, catalyzed by DNA methyltransferases (DNMTs), is associated with not only various cancers by silencing of tumor suppressor genes but also other diseases. The DNMTs, especially the DNMT1, DNMT3A and DNMT3B, are often overexpressed in various canc …

2022年7月15日 · Shinichi Mizuno et al. analysed DNMTs expression levels of 33 AML cases by competitive PCR and found that DNMT1 was expressed at a high level in most AML cases. Overexpression of DNMT1 could be associated with the development and relapse of AML triggered by hypermethylation of tumour suppressor genes [ Citation 61 ].

2015年3月2日 · A/E and HIF1α shape a positive regulatory loop and cooperate to upregulate DNMT3a expression leading to a DNA hypermethylation profile in AML, which is different from existing views emphasizing...

5 天之前 · This process is regulated by DNA methyltransferases (DNMTs), which alter chromatin’s structure to modulate expression . Aberrant DNA methylation is a hallmark of carcinogenesis, as irregular methylation leads to the silencing of tumor-suppressor genes and …

2020年7月20日 · Accumulating evidence demonstrates that regulation of DNA methylation by DNMTs is critical for normal hematopoiesis. Aberrant DNA methylation due to DNMT dysregulation and mutations is known as an important molecular event of hematological malignancies, such as DNMT3A mutations in acute myeloid leukemia.

1 天前 · The epigenetic changes often prime the cells to be more susceptible for additional cytotoxic treatments and may reverse acquired resistance. 166,171,172,173 Most DNMTs impact the BCL2 proteins by ...