ArticleNeoplasia (New York, N.Y.)2018
Genetic and Epigenetic Perturbations by DNMT3A-R882 Mutants Impaired Apoptosis through Augmentation of PRDX2 in Myeloid Leukemia Cells.
Article in Neoplasia (New York, N.Y.), 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 24 citations in OpenAlex.
- Mutant calreticulin enables potent and selective CAR-T cell therapy in preclinical models of myeloproliferative neoplasms.Journal for immunotherapy of cancer · 2026Article
- Overexpression of PRDX2 alleviates chronic thromboembolic pulmonary hypertension by modulating inflammation and mitophagy.Scientific reports · 2025Article
- circKCNQ5 promotes the proliferation of DNA-methyltransferase 3A R882 mutated acute myeloid leukemia cells by elevating high-mobility group box 1 expression.Annals of medicine · 2025Article
- CD44v6 CAR-T Cells Target DNMT3A-Mutant AML: Synergistic Enhancement by Decitabine.Current medical science · 2025Article
- DNMT3A-R882 mutation promotes acute myeloid leukemia progression by recruiting E2H2 to inhibit circKCNQ5 methylation.Discover oncology · 2025Article
- Targeting Nrf2 in acute myeloid leukemia: an updated review on its role in chemoresistance and emerging therapeutic strategies.Medical oncology (Northwood, London, England) · 2025Review
- Development of a cuproptosis-related prognostic signature to reveal heterogeneity of the immune microenvironment and drug sensitivity in acute lymphoblastic leukemia.European journal of medical research · 2025Article
- Biological Features of KLC2 Mutations in Chronic Myeloid Leukemia and Their Contribution to Inducing Drug Resistance.Oncology research · 2025Article
- Article
- Epigenetic regulation in hematopoiesis and its implications in the targeted therapy of hematologic malignancies.Signal transduction and targeted therapy · 2023Review
- DNMT3A R882H mutation drives daunorubicin resistance in acute myeloid leukemia via regulating NRF2/NQO1 pathway.Cell communication and signaling : CCS · 2022Article
- Epigenetic signatures in cancer: proper controls, current challenges and the potential for clinical translation.Genome medicine · 2021Review
- Study on the Immune Escape Mechanism of Acute Myeloid Leukemia With DNMT3A Mutation.Frontiers in immunology · 2021Article
- The Influence of Methylating Mutations on Acute Myeloid Leukemia: Preliminary Analysis on 56 Patients.Diagnostics (Basel, Switzerland) · 2020Article
- DNMT3A mutants provide proliferating advantage with augmentation of self-renewal activity in the pathogenesis of AML in KMT2A-PTD-positive leukemic cells.Oncogenesis · 2020Article
- PRDX2 protects against oxidative stress induced by H. pylori and promotes resistance to cisplatin in gastric cancer.Redox biology · 2020Article
- Azelaic Acid Exerts Antileukemia Effects against Acute Myeloid Leukemia by Regulating the Prdxs/ROS Signaling Pathway.Oxidative medicine and cellular longevity · 2020Article
- Article
- RUNX1 mutations promote leukemogenesis of myeloid malignancies in ASXL1-mutated leukemia.Journal of hematology & oncology · 2019Article
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Authors and funding
6 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
DNA methyltransferase 3A (DNMT3A) is mutated in various myeloid neoplasms including acute myeloid leukemia (AML), especially at the Arg882 and associated with inferior outcomes. Here, we report that the DNMT3A-Arg882His/Cys (R882H/C) mutations led to inactivation of apoptosis through DNA damage signaling following the impairment of differentiation of myeloid leukemia cells. Gene expression profiling analysis revealed aberrant expression of several cell-cycle and apoptosis-related genes, and the DNA methylation assay identified both hypo- and hypermethylation features in different regions throughout the whole genome of DNMT3A mutants-transduced myeloid cells. We found that DNMT3A-R882H/C mutations upregulated the expression of an antioxidant protein, pyroxiredoxin-2 (PRDX2), at the mRNA and protein levels with decreased accumulation of reactive oxygen species (ROS). Augmentation of ROS generation by ROS accumulating agent or by knockdown of PRDX2 from myeloid cells effectively increased drug sensitivity and apoptosis as a consequence of reduced cell proliferation. DNMT3A-R882C/H mutations decreased apoptosis induction in part by increasing the antioxidant capacity of the cell owing to upregulation of PRDX2. Molecularly, both DNMT3A-WT and R882H/C mutants interacted with PRDX2; and R882C/H mutation-induced hypomethylation increased PRDX2 expression which enhanced cell proliferation and growth with impairment of apoptosis, thereby contributing to leukemogenesis.
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