ArticleJCI insight2023
Loss of Dnmt3a impairs hematopoietic homeostasis and myeloid cell skewing via the PI3Kinase pathway.
Article in JCI insight, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.
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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
9 citing papers in PubMed, 7 citations in OpenAlex.
- Loss of Function Dnmt3a Mutation Leads to Aberrant Neutrophil Migration.Experimental hematology · 2026Article
- Clonal Hematopoiesis in Colorectal Cancer: Mechanisms and Implications.Cancer medicine · 2026Review
- Current Understanding of CHIP's Immunobiological Footprint with A Focus on Gastrointestinal Disorders: A Review of the Literature.Current oncology reports · 2026Review
- Genome-Wide CRISPR Screen Reveals PIK3CA Inhibition Enhances Lipid Nanoparticle-Mediated siRNA Delivery.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Acute myeloid leukemia with plasmacytoid dendritic cell proliferation: A case report and literature review.Oncology letters · 2025Article
- ST2/IL-33 axis blockade inhibits regulatory T cell cytotoxicity towards CD8 T cells in the leukemic niche.Nature communications · 2025Article
- Targeting Calprotectin S100A8/A9 to Overcome AML Progression in DNMT3A-Mutant Cells.Current medical science · 2025Article
- [CLAG±DAC regimen in the treatment of refractory/relapsed acute myeloid leukemia].Zhonghua xue ye xue za zhi = Zhonghua xueyexue zazhi · 2024Article
- Investigating resistance to 5-Azacytidine and Venetoclax in PDX models of MDS/AML.Frontiers in oncology · 2024Article
Corrections and comments
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Authors and funding
13 authors at 3 institutions in 1 country.
Funding
Abstract
Loss-of-function mutations in the DNA methyltransferase 3A (DNMT3A) are seen in a large number of patients with acute myeloid leukemia (AML) with normal cytogenetics and are frequently associated with poor prognosis. DNMT3A mutations are an early preleukemic event, which - when combined with other genetic lesions - result in full-blown leukemia. Here, we show that loss of Dnmt3a in hematopoietic stem and progenitor cells (HSC/Ps) results in myeloproliferation, which is associated with hyperactivation of the phosphatidylinositol 3-kinase (PI3K) pathway. PI3Kα/β or the PI3Kα/δ inhibitor treatment partially corrects myeloproliferation, although the partial rescue is more efficient in response to the PI3Kα/β inhibitor treatment. In vivo RNA-Seq analysis on drug-treated Dnmt3a-/- HSC/Ps showed a reduction in the expression of genes associated with chemokines, inflammation, cell attachment, and extracellular matrix compared with controls. Remarkably, drug-treated leukemic mice showed a reversal in the enhanced fetal liver HSC-like gene signature observed in vehicle-treated Dnmt3a-/- LSK cells as well as a reduction in the expression of genes involved in regulating actin cytoskeleton-based functions, including the RHO/RAC GTPases. In a human PDX model bearing DNMT3A mutant AML, PI3Kα/β inhibitor treatment prolonged their survival and rescued the leukemic burden. Our results identify a potentially new target for treating DNMT3A mutation-driven myeloid malignancies.
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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 Socratic graph.