ArticleOncotarget2017
Novel impact of the DNMT3A R882H mutation on GSH metabolism in a K562 cell model established by TALENs.
Article in Oncotarget, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed, 28 citations in OpenAlex.
- DNMT3A in cancer: from epigenetic writer to oncogenic driver.Clinical epigenetics · 2026Review
- Serine metabolism reprogramming in cancer: a multi-tiered regulatory framework.Acta biochimica et biophysica Sinica · 2025Review
- SubTuner leverages physics-based modeling to complement AI in enzyme engineering toward non-native substrates.Chem catalysis · 2025Article
- XPO1 inhibition displays anti-leukemia efficacy against DNMT3A-mutant acute myeloid leukemia via downregulating glutathione pathway.Annals of hematology · 2024Article
- Transcriptome and Metabolome Analyses Provide Insight into the Glucose-Induced Adipogenesis in Porcine Adipocytes.Current issues in molecular biology · 2024Article
- Genomics and transcriptomic alterations of the glutamate receptors in acute myeloid leukemia.Clinical and translational science · 2023Article
- DNMT3A mutation promotes leukemia development through NAM-NAD metabolic reprogramming.Journal of translational medicine · 2023Article
- Identification of potential ferroptosis hub genes in acute-on-chronic liver failure based on bioinformatics analysis and experimental verification.BMC medical genomics · 2023Article
- Identification of three novel DNMT3A mutations with compromising methylation capacity in human acute myeloid leukaemia.Molecular biology reports · 2022Article
- The ins and outs of serine and glycine metabolism in cancer.Nature metabolism · 2021Review
- Study on the Immune Escape Mechanism of Acute Myeloid Leukemia With DNMT3A Mutation.Frontiers in immunology · 2021Article
- Inhibitory effect of alpinetin on IL-6 expression by promoting cytosine methylation in CpG islands in the IL-6 promoter region.Molecular genetics & genomic medicine · 2020Article
- Understanding the R882H mutation effects of DNA methyltransferase DNMT3A: a combination of molecular dynamics simulations and QM/MM calculations.RSC advances · 2019Article
Corrections and comments
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Authors and funding
12 authors at 7 institutions in 1 country.
Funding
Abstract
DNA methyltransferase 3A (DNMT3A) mutations occurred in 18%~23% of acute myeloid leukemia (AML) patients, and were considered to be an adverse prognostic factor for adult de novo AML cases. However, the relevant molecular mechanism of the mutation in AML pathogenesis remains obscure. In this study, we established K562 and SKM1 cell model carrying the DNMT3A R882H mutation via transcription activator-like effector nuclease (TALEN) and Clustered regularly interspaced short palindromic repeats (CRISPR/Cas9) technology, and discovered that mutated DNMT3A could promote the proliferative capability of malignant cell clones. Further RNA microarray analysis revealed that some genes crucial for glutathione (GSH) synthesis, including CTH, PSPH, PSAT1 and especially SLC7A11 (the cysteine/glutamate transporter) were significantly up-regulated, which resulted in significant elevation of intracellular GSH levels. A subsequent experiment demonstrated that the mutant clones are resistant to chemotherapy as well as SLC7A11-inhibitorsBy shRNA induced SLC7A11 silencing, we discovered profoundly decreased cellular GSH and cell proliferative ability of DNMT3A mutated clones. Our results provided novel insight into the role of the DNMT3A R882H mutation in AML pathogenesis and suggested that targeting the cellular GSH synthetic pathway could enhance the current therapy for AML patients with the DNMT3A R882H mutation.
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