ArticleNature communications2016
DNMT3A R882 mutants interact with polycomb proteins to block haematopoietic stem and leukaemic cell differentiation.
Article in Nature communications, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 57 papers.
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Who cites it
57 citing papers in PubMed, 100 citations in OpenAlex.
- Article
- DNA methyltransferase inhibitors in oncology: clinical progress, limitations and future directions.Epigenomics · 2026Review
- Multiomic analysis of clonal development reveals new regulators of leukemic cell growth.Genes & development · 2026Article
- Review
- PRC2-Related Epigenetic Age Acceleration in Acute Myeloid Leukemia with DNMT3A and IDH2 Mutations.Advanced biology · 2026Article
- The Immunological Consequences of Clonal Hematopoiesis in Heart Failure.Immunological reviews · 2026Review
- Dysregulation of HOXA genes in acute myeloid leukemia and targeted therapy.NPJ precision oncology · 2025Review
- Clonal hematopoiesis of indeterminate potential: a multisystem hub bridging hematopoietic dysfunction with non-hematopoietic diseases.Military Medical Research · 2025Review
- Targeting Nrf2 in acute myeloid leukemia: an updated review on its role in chemoresistance and emerging therapeutic strategies.Medical oncology (Northwood, London, England) · 2025Review
- Epigenetic regulation of cancer stemness.Signal transduction and targeted therapy · 2025Review
- From genotype to phenotype: decoding mutations in blasts by holo-tomographic flow cytometry.Light, science & applications · 2025Article
- Article
- Significance of targeting DNMT3A mutations in AML.Annals of hematology · 2025Review
- Hypoxia impairs decitabine-induced expression of HLA-DR in acute myeloid leukaemia cell lines.Clinical epigenetics · 2025Article
- Pharmacological targeting of CBX7 alters the epigenetic landscape and induces differentiation of leukemic cells.Blood neoplasia · 2024Article
- Epigenetic modulators provide a path to understanding disease and therapeutic opportunity.Genes & development · 2024Review
- Structure-guided functional suppression of AML-associated DNMT3A hotspot mutations.Nature communications · 2024Article
- Rapid and accurate remethylation of DNA inScience advances · 2024Article
- HOXA9 Regulome and Pharmacological Interventions in Leukemia.Advances in experimental medicine and biology · 2024Review
- [Effect of clonal hematopoiesis in remission on hematopoiesis recovery in patients with NPM1 mutated acute myeloid leukemia after chemotherapy].Zhonghua xue ye xue za zhi = Zhonghua xueyexue zazhi · 2023Article
Corrections and comments
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Authors and funding
11 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Despite the clinical impact of DNMT3A mutation on acute myeloid leukaemia, the molecular mechanisms regarding how this mutation causes leukaemogenesis in vivo are largely unknown. Here we show that, in murine transplantation experiments, recipients transplanted with DNMT3A mutant-transduced cells exhibit aberrant haematopoietic stem cell (HSC) accumulation. Differentiation-associated genes are downregulated without accompanying changes in methylation status of their promoter-associated CpG islands in DNMT3A mutant-transduced stem/progenitor cells, representing a DNA methylation-independent role of mutated DNMT3A. DNMT3A R882H also promotes monoblastic transformation in vitro in combination with HOXA9. Molecularly, the DNMT3A mutant interacts with polycomb repressive complex 1 (PRC1), causing transcriptional silencing, revealing a DNA methylation-independent role of DNMT3A mutation. Suppression of PRC1 impairs aberrant HSC accumulation and monoblastic transformation. From our data, it is shown that DNMT3A mutants can block the differentiation of HSCs and leukaemic cells via PRC1. This interaction could be targetable in DNMT3A-mutated leukaemias.
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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.