ArticleBlood2015
Enforced differentiation of Dnmt3a-null bone marrow leads to failure with c-Kit mutations driving leukemic 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 63 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.
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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
63 citing papers in PubMed, 94 citations in OpenAlex.
- DNMT3A R882H Is Not Required for Disease Maintenance in Primary Human AML but Is Associated with Increased Leukemia Stem Cell Frequency.Cancer discovery · 2026Article
- Non-canonical functions of DNMT3A in hematopoietic stem cells regulate telomerase activity and genome integrity.Cell stem cell · 2025Article
- Identification of HOXA9 methylation as an epigenetic biomarker predicting prognosis and guiding treatment choice in acute myeloid leukemia.BMC cancer · 2025Article
- Dose-dependent effects of Dnmt3a in an inducible murine model of KrasExperimental hematology · 2024Article
- Epigenetic Modification of Cytosines in Hematopoietic Differentiation and Malignant Transformation.International journal of molecular sciences · 2023Review
- Emerging Roles of Epigenetic Regulators in Maintaining Hematopoietic Stem Cell Homeostasis.Advances in experimental medicine and biology · 2023Article
- Noncoding rules of survival: epigenetic regulation of normal and malignant hematopoiesis.Frontiers in molecular biosciences · 2023Review
- Hematopoietic differentiation persists in human iPSCs defective in de novo DNA methylation.BMC biology · 2022Article
- Clonal hematopoiesis: Mutation-specific adaptation to environmental change.Cell stem cell · 2022Review
- Maladaptive trained immunity and clonal hematopoiesis as potential mechanistic links between periodontitis and inflammatory comorbidities.Periodontology 2000 · 2022Review
- Txnip Enhances Fitness of Dnmt3a-Mutant Hematopoietic Stem Cells via p21.Blood cancer discovery · 2022Article
- Perturbed hematopoiesis in individuals with germline DNMT3A overgrowth Tatton-Brown-Rahman syndrome.Haematologica · 2022Article
- Review
- Molecular Characterization of a First-in-Human Clinical Response to Nimesulide in Acute Myeloid Leukemia.Frontiers in oncology · 2022Article
- Murine Models of Acute Myeloid Leukemia.Frontiers in oncology · 2022Review
- Emerging role of different DNA methyltransferases in the pathogenesis of cancer.Frontiers in pharmacology · 2022Review
- Activation ofCancer research · 2021Article
- Review
- Clonal Hematopoiesis: From Mechanisms to Clinical Intervention.Cancer discovery · 2021Review
- Functional and epigenetic phenotypes of humans and mice with DNMT3A Overgrowth Syndrome.Nature communications · 2021Article
3 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
10 authors at 3 institutions in 2 countries.
Funding
Abstract
Genome sequencing studies of patient samples have implicated the involvement of various components of the epigenetic machinery in myeloid diseases, including the de novo DNA methyltransferase DNMT3A. We have recently shown that Dnmt3a is essential for hematopoietic stem cell differentiation. Here, we investigated the effect of loss of Dnmt3a on hematopoietic transformation by forcing the normally quiescent hematopoietic stem cells to divide in vivo. Mice transplanted with Dnmt3a-null bone marrow in the absence of wildtype support cells succumbed to bone marrow failure (median survival, 328 days) characteristic of myelodysplastic syndromes with symptoms including anemia, neutropenia, bone marrow hypercellularity, and splenomegaly with myeloid infiltration. Two out of 25 mice developed myeloid leukemia with >20%blasts in the blood and bone marrow. Four out of 25 primary mice succumbed to myeloproliferative disorders, some of which progressed to secondary leukemia after long latency. Exome sequencing identified cooperating c-Kit mutations found only in the leukemic samples. Ectopic introduction of c-Kit variants into a Dnmt3a-deficient background produced acute leukemia with a short latency (median survival, 67 days). Our data highlight crucial roles of Dnmt3a in normal and malignant hematopoiesis and suggest that a major role for this enzyme is to facilitate developmental progression of progenitor cells at multiple decision checkpoints.
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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.