ArticleLeukemia2016
Dnmt3a regulates myeloproliferation and liver-specific expansion of hematopoietic stem and progenitor cells.
Article in Leukemia, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 57 papers, 1 of them a synthesis that pooled it.
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
57 citing papers in PubMed, 1 synthesis or guideline pooled it, 73 citations in OpenAlex.
- The Coming of Age of Preclinical Models of MDS.Frontiers in oncology · 2022Pooled it
- Clonal hematopoiesis of indeterminate potential (CHIP)-a pivotal contributor of aging and related disorders.Annals of translational medicine · 2026Review
- Aberrant Kupffer-like differentiation of hematopoietic stem cell is critical for the MDS pathogenesis in Setd2-deficient mice.Cell death and differentiation · 2026Article
- Clonal Haematopoiesis in Type 2 Diabetes: A Review of Mechanistic Links With Inflammation and Cardiovascular Disease.Diabetes/metabolism research and reviews · 2026Review
- Mutation Patterns Define Clinical Heterogeneity in Acute Myeloid Leukemia.Journal of Cancer · 2026Article
- Myelodysplastic Neoplasms (MDS): Pathogenesis and Therapeutic Prospects.Biomolecules · 2025Review
- Hypermethylation of DNA impairs megakaryogenesis in delayed platelet recovery after allogeneic hematopoietic stem cell transplantation.Science advances · 2025Article
- STING mediates increased self-renewal and lineage skewing in DNMT3A-mutated hematopoietic stem/progenitor cells.Leukemia · 2025Article
- Tissue-specific roles of de novo DNA methyltransferases.Epigenetics & chromatin · 2025Review
- Article
- Hematopoietic aging promotes cancer by fueling IL-1⍺-driven emergency myelopoiesis.Science (New York, N.Y.) · 2024Article
- Chronic TNF in the aging microenvironment exacerbates Tet2 loss-of-function myeloid expansion.Blood advances · 2024Article
- Role of reactive oxygen species in myelodysplastic syndromes.Cellular & molecular biology letters · 2024Review
- Hematopoietic-specific heterozygous loss of Dnmt3a exacerbates colitis-associated colon cancer.The Journal of experimental medicine · 2023Article
- Genotoxic aldehyde stress prematurely ages hematopoietic stem cells in a p53-driven manner.Molecular cell · 2023Article
- Loss of Dnmt3a impairs hematopoietic homeostasis and myeloid cell skewing via the PI3Kinase pathway.JCI insight · 2023Article
- Pediatric Myeloid Sarcoma, More than Just a Chloroma: A Review of Clinical Presentations, Significance, and Biology.Cancers · 2023Review
- Epigenetic Modification of Cytosines in Hematopoietic Differentiation and Malignant Transformation.International journal of molecular sciences · 2023Review
- Clonal hematopoiesis, somatic mosaicism, and age-associated disease.Physiological reviews · 2023Review
- miR-196b-TLR7/8 Signaling Axis Regulates Innate Immune Signaling and Myeloid Maturation in DNMT3A-Mutant AML.Clinical cancer research : an official journal of the American Association for Cancer Research · 2022Article
Corrections and comments
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Authors and funding
22 authors at 5 institutions in 2 countries.
Funding
Abstract
DNA methyltransferase 3A (DNMT3A) mutations are observed in myeloid malignancies, including myeloproliferative neoplasms (MPN), myelodysplastic syndromes (MDS) and acute myeloid leukemia (AML). Transplantation studies have elucidated an important role for Dnmt3a in stem cell self-renewal and in myeloid differentiation. Here, we investigated the impact of conditional hematopoietic Dnmt3a loss on disease phenotype in primary mice. Mx1-Cre-mediated Dnmt3a ablation led to the development of a lethal, fully penetrant MPN with myelodysplasia (MDS/MPN) characterized by peripheral cytopenias and by marked, progressive hepatomegaly. We detected expanded stem/progenitor populations in the liver of Dnmt3a-ablated mice. The MDS/MPN induced by Dnmt3a ablation was transplantable, including the marked hepatomegaly. Homing studies showed that Dnmt3a-deleted bone marrow cells preferentially migrated to the liver. Gene expression and DNA methylation analyses of progenitor cell populations identified differential regulation of hematopoietic regulatory pathways, including fetal liver hematopoiesis transcriptional programs. These data demonstrate that Dnmt3a ablation in the hematopoietic system leads to myeloid transformation in vivo, with cell-autonomous aberrant tissue tropism and marked extramedullary hematopoiesis (EMH) with liver involvement. Hence, in addition to the established role of Dnmt3a in regulating self-renewal, Dnmt3a regulates tissue tropism and limits myeloid progenitor expansion in vivo.
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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.