ArticleThe Journal of clinical investigation2017
Haploinsufficiency for DNA methyltransferase 3A predisposes hematopoietic cells to myeloid malignancies.
Article in The Journal of clinical investigation, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 61 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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Who cites it
61 citing papers in PubMed, 89 citations in OpenAlex.
- Efferocytosis activates a DNMT3A-mediated oxidized DNA repair pathway to enable tissue resolution.The Journal of clinical investigation · 2026Article
- Glioma-induced DNMT3A reduction in microglia promotes an anti-tumoral phenotype.Cell death and differentiation · 2026Article
- Clonal hematopoiesis-associated DNMT3A mutations derepress bivalent Polycomb target genes and enhance macrophage migration.bioRxiv : the preprint server for biology · 2026Article
- Loss of Function Dnmt3a Mutation Leads to Aberrant Neutrophil Migration.Experimental hematology · 2026Article
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- Increased local DNA methylation disorder in AMLs with DNMT3A-destabilizing variants and its clinical implication.Nature communications · 2025Article
- Rapid and accurate remethylation of DNA inScience advances · 2024Article
- Clonal hematopoiesis with DNMT3A mutation is associated with lower white matter hyperintensity volume.CNS neuroscience & therapeutics · 2023Article
- Inflammatory signals from fatty bone marrow support DNMT3A driven clonal hematopoiesis.Nature communications · 2023Article
- Melanoma in a patient with DNMT3A overgrowth syndrome.Cold Spring Harbor molecular case studies · 2023Article
- Epigenetic Modification of Cytosines in Hematopoietic Differentiation and Malignant Transformation.International journal of molecular sciences · 2023Review
- Genomic Aging, Clonal Hematopoiesis, and Cardiovascular Disease.Arteriosclerosis, thrombosis, and vascular biology · 2023Review
- Clonal hematopoiesis, somatic mosaicism, and age-associated disease.Physiological reviews · 2023Review
- Identification of three novel DNMT3A mutations with compromising methylation capacity in human acute myeloid leukaemia.Molecular biology reports · 2022Article
- Pseudo-mutant P53 is a unique phenotype ofHaematologica · 2022Article
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- Hematopoietic differentiation persists in human iPSCs defective in de novo DNA methylation.BMC biology · 2022Article
- 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
1 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
16 authors at 3 institutions in 1 country.
Funding
Abstract
The gene that encodes de novo DNA methyltransferase 3A (DNMT3A) is frequently mutated in acute myeloid leukemia genomes. Point mutations at position R882 have been shown to cause a dominant negative loss of DNMT3A methylation activity, but 15% of DNMT3A mutations are predicted to produce truncated proteins that could either have dominant negative activities or cause loss of function and haploinsufficiency. Here, we demonstrate that 3 of these mutants produce truncated, inactive proteins that do not dimerize with WT DNMT3A, strongly supporting the haploinsufficiency hypothesis. We therefore evaluated hematopoiesis in mice heterozygous for a constitutive null Dnmt3a mutation. With no other manipulations, Dnmt3a+/- mice developed myeloid skewing over time, and their hematopoietic stem/progenitor cells exhibited a long-term competitive transplantation advantage. Dnmt3a+/- mice also spontaneously developed transplantable myeloid malignancies after a long latent period, and 3 of 12 tumors tested had cooperating mutations in the Ras/MAPK pathway. The residual Dnmt3a allele was neither mutated nor downregulated in these tumors. The bone marrow cells of Dnmt3a+/- mice had a subtle but statistically significant DNA hypomethylation phenotype that was not associated with gene dysregulation. These data demonstrate that haploinsufficiency for Dnmt3a alters hematopoiesis and predisposes mice (and probably humans) to myeloid malignancies by a mechanism that is not yet clear.
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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.