ArticleBlood2015
Dnmt3a loss predisposes murine hematopoietic stem cells to malignant transformation.
Article in Blood, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 163 papers, 1 of them a synthesis that pooled it.
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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.
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Who cites it
163 citing papers in PubMed, 1 synthesis or guideline pooled it, 232 citations in OpenAlex.
- The metabolic addiction of cancer stem cells.Frontiers in oncology · 2022Pooled it
- Sustained clonal hematopoiesis by HLA-lacking hematopoietic stem cells without driver mutations in aplastic anemia.Blood advances · 2018Trial
- Developmental timing distinguishes pediatric and adult cancers through retention and rewiring mechanisms.Nature communications · 2026Review
- Clonal hematopoiesis of indeterminate potential (CHIP)-a pivotal contributor of aging and related disorders.Annals of translational medicine · 2026Review
- P300/CBP inhibition with inobrodib in combination with gilteritinib and venetoclax targets leukemia stem cells in epigenetic mutant AML.Science advances · 2026Article
- Mechanisms of DNA methyltransferase 3A1-mediated DNA methylation of nucleosomes.The Journal of biological chemistry · 2026Article
- Clonal haematopoiesis in chronic lymphocytic leukaemia: Biology, inflammaging and clinical implications in the era of targeted therapy.Clinical and translational medicine · 2026Review
- DNMT3A p.R882C driven proliferation and anti-apoptotic effects in pancreatic cancer cells.Scientific reports · 2026Article
- The role of epigenetic modifications in hematological cancers.Frontiers in oncology · 2026Review
- Humanized mouse models in MDS.Cell death & disease · 2025Review
- Direct genetic transformation bypasses tumor-associated DNA methylation alterations.Genome biology · 2025Article
- Hallmarks of stem cell aging.Cell stem cell · 2025Review
- Article
- DNMT3A facilitates breast cancer progression via regulating ADAMTS8 mediated EGFR-MEK-ERK activation.PloS one · 2025Article
- Review
- Emerging insights into epigenetics and hematopoietic stem cell trafficking in age-related hematological malignancies.Stem cell research & therapy · 2024Review
- Age-associated clonal B cells drive B cell lymphoma in mice.Nature aging · 2024Article
- Dose-dependent effects of Dnmt3a in an inducible murine model of KrasExperimental hematology · 2024Article
- RAS mutations in myeloid malignancies: revisiting old questions with novel insights and therapeutic perspectives.Blood cancer journal · 2024Review
- High-risk and silent clonal hematopoietic genotypes in patients with nonhematologic cancer.Blood advances · 2024Article
103 more citing papers are in PubMed but not listed here.
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Authors and funding
11 authors at 3 institutions in 1 country.
Funding
Abstract
DNA methyltransferase 3A (DNMT3A) is mutated in hematologic malignancies affecting myeloid, mixed, and lymphoid lineages, and these mutations are associated with poor prognosis. Past studies in mice revealed Dnmt3a-knockout (KO)hematopoietic stem cells (HSCs) had increased self-renewal, but no leukemia was observed. Here, all lethally irradiated mice transplanted with Dnmt3a-deleted HSCs died within 1 year. Animals were diagnosed with a spectrum of malignancies similar to those seen in patients with DNMT3A mutations, including myelodysplastic syndrome, acute myeloid leukemia, primary myelofibrosis, and T- and B-cell acute lymphocytic leukemia. In some cases, acquired malignancies exhibited secondary mutations similar to those identified in patients. Loss of Dnmt3a led to disturbed methylation patterns that were distinct in lymphoid and myeloid disease, suggesting lineage-specific methylation aberrations promoted by Dnmt3a loss. Global hypomethylation was observed in all of the malignancies, but lymphoid malignancies also exhibited hypermethylation, particularly at promoter regions. This mouse model underscores the important role of Dnmt3a in normal hematopoietic development and demonstrates that Dnmt3a loss of function confers a preleukemic phenotype on murine HSCs. This model may serve as a tool to study DNMT3A mutation associated malignancies and for developing targeted strategies for eliminating preleukemic cells for prevention and treatment of hematologic malignancies in the future.
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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.