ArticleBlood2020
Dnmt3a loss and Idh2 neomorphic mutations mutually potentiate malignant hematopoiesis.
Article in Blood, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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Who cites it
26 citing papers in PubMed.
- Clinical Characteristics, Gene Mutation Profiles and Prognosis of Patients With Acute Myeloid Leukemia Carrying PHF6 Mutations.Cancer medicine · 2026Article
- Synergistic intragenic epigenetic deregulation by IDH2 and SRSF2 mutations causes mis-splicing of key transcriptional regulators.Science advances · 2026Article
- Deconvoluting clonal and cellular architecture in IDH-mutant acute myeloid leukemia.Cell stem cell · 2025Article
- Prognostic impact of co-mutations in adults withBlood science (Baltimore, Md.) · 2025Article
- STING mediates increased self-renewal and lineage skewing in DNMT3A-mutated hematopoietic stem/progenitor cells.Leukemia · 2025Article
- Double mutant DNMT3A AML: a unique subtype experiencing increased DNA damage and poor prognosis.Blood advances · 2025Article
- Significance of targeting DNMT3A mutations in AML.Annals of hematology · 2025Review
- Carrier-Free Peptide-Daunorubicin-Small Interfering RNA Nanoassembly for Targeted Therapy of Acute Myeloid Leukemia.Cyborg and bionic systems (Washington, D.C.) · 2025Article
- Landscape of biallelic DNMT3A mutant myeloid neoplasms.Journal of hematology & oncology · 2024Article
- Transgenic IDH2Oncogene · 2023Article
- Epigenetic regulation in hematopoiesis and its implications in the targeted therapy of hematologic malignancies.Signal transduction and targeted therapy · 2023Review
- The Immuno-Oncology and Genomic Aspects of DNA-Hypomethylating Therapeutics in Acute Myeloid Leukemia.International journal of molecular sciences · 2023Review
- MIR retrotransposons link the epigenome and the transcriptome of coding genes in acute myeloid leukemia.Nature communications · 2022Article
- Transcriptome-wide subtyping of pediatric and adult T cell acute lymphoblastic leukemia in an international study of 707 cases.Proceedings of the National Academy of Sciences of the United States of America · 2022Article
- Role of mJournal of clinical laboratory analysis · 2022Article
- Oncogenesis induced by combined Phf6 and Idh2 mutations through increased oncometabolites and impaired DNA repair.Oncogene · 2022Article
- Murine Models of Acute Myeloid Leukemia.Frontiers in oncology · 2022Review
- Driver mutations of intrahepatic cholangiocarcinoma shape clinically relevant genomic clusters with distinct molecular features and therapeutic vulnerabilities.Theranostics · 2022Article
- Review
- Clonal hematopoiesis and associated diseases: A review of recent findings.Cancer science · 2021Review
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14 authors.
Funding
Abstract
Mutations in the epigenetic regulators DNMT3A and IDH1/2 co-occur in patients with acute myeloid leukemia and lymphoma. In this study, these 2 epigenetic mutations cooperated to induce leukemia. Leukemia-initiating cells from Dnmt3a-/- mice that express an IDH2 neomorphic mutant have a megakaryocyte-erythroid progenitor-like immunophenotype, activate a stem-cell-like gene signature, and repress differentiated progenitor genes. We observed an epigenomic dysregulation with the gain of repressive H3K9 trimethylation and loss of H3K9 acetylation in diseased mouse bone marrow hematopoietic stem and progenitor cells (HSPCs). HDAC inhibitors rapidly reversed the H3K9 methylation/acetylation imbalance in diseased mouse HSPCs while reducing the leukemia burden. In addition, using targeted metabolomic profiling for the first time in mouse leukemia models, we also showed that prostaglandin E2 is overproduced in double-mutant HSPCs, rendering them sensitive to prostaglandin synthesis inhibition. These data revealed that Dnmt3a and Idh2 mutations are synergistic events in leukemogenesis and that HSPCs carrying both mutations are sensitive to induced differentiation by the inhibition of both prostaglandin synthesis and HDAC, which may reveal new therapeutic opportunities for patients carrying IDH1/2 mutations.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.