ArticleCell stem cell2020
Tissue-Biased Expansion of DNMT3A-Mutant Clones in a Mosaic Individual Is Associated with Conserved Epigenetic Erosion.
Article in Cell stem cell, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
21 citing papers in PubMed, 32 citations in OpenAlex.
- Clonal Hematopoiesis in Colorectal Cancer: Mechanisms and Implications.Cancer medicine · 2026Review
- Posttransplantation clonal dynamics of hematopoietic stem cells carrying prenatal and early-lifeHemaSphere · 2025Article
- Human embryonic genetic mosaicism and its effects on development and disease.Nature reviews. Genetics · 2024Review
- Identification of leukemia stem cell subsets with distinct transcriptional, epigenetic and functional properties.Leukemia · 2024Article
- Review
- Crosstalk between DNA methylation and hypoxia in acute myeloid leukaemia.Clinical epigenetics · 2023Review
- The meaning of adaptation in aging: insights from cellular senescence, epigenetic clocks and stem cell alterations.Nature aging · 2023Review
- Article
- Single-cell multi-omics of human clonal hematopoiesis reveals that DNMT3A R882 mutations perturb early progenitor states through selective hypomethylation.Nature genetics · 2022Article
- Mechanisms of T cell exhaustion guiding next-generation immunotherapy.Trends in cancer · 2022Review
- Clonal Hematopoiesis and Mosaicism Revealed by a Multi-Tissue Analysis of Constitutional TP53 Status.Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology · 2022Article
- Constitutive loss of DNMT3A causes morbid obesity through misregulation of adipogenesis.eLife · 2022Article
- Perturbed hematopoiesis in individuals with germline DNMT3A overgrowth Tatton-Brown-Rahman syndrome.Haematologica · 2022Article
- DNMT3A Harboring Leukemia-Associated Mutations Directs Sensitivity to DNA Damage at Replication Forks.Clinical cancer research : an official journal of the American Association for Cancer Research · 2022Article
- Lessons From Pediatric MDS: Approaches to Germline Predisposition to Hematologic Malignancies.Frontiers in oncology · 2022Review
- Deleting DNMT3A in CAR T cells prevents exhaustion and enhances antitumor activity.Science translational medicine · 2021Article
- Functional and epigenetic phenotypes of humans and mice with DNMT3A Overgrowth Syndrome.Nature communications · 2021Article
- DNMT3A haploinsufficiency causes dichotomous DNA methylation defects at enhancers in mature human immune cells.The Journal of experimental medicine · 2021Article
- Somatic mosaicism in inherited bone marrow failure syndromes.Best practice & research. Clinical haematology · 2021Review
- Alterations toCancer research · 2021Review
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Authors and funding
24 authors at 8 institutions in 3 countries.
Funding
Abstract
DNA methyltransferase 3A (DNMT3A) is the most commonly mutated gene in clonal hematopoiesis (CH). Somatic DNMT3A mutations arise in hematopoietic stem cells (HSCs) many years before malignancies develop, but difficulties in comparing their impact before malignancy with wild-type cells have limited the understanding of their contributions to transformation. To circumvent this limitation, we derived normal and DNMT3A mutant lymphoblastoid cell lines from a germline mosaic individual in whom these cells co-existed for nearly 6 decades. Mutant cells dominated the blood system, but not other tissues. Deep sequencing revealed similar mutational burdens and signatures in normal and mutant clones, while epigenetic profiling uncovered the focal erosion of DNA methylation at oncogenic regulatory regions in mutant clones. These regions overlapped with those sensitive to DNMT3A loss after DNMT3A ablation in HSCs and in leukemia samples. These results suggest that DNMT3A maintains a conserved DNA methylation pattern, the erosion of which provides a distinct competitive advantage to hematopoietic cells.
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Registered trials
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.