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December 8, 2025BloodOpen Access

DNMT3A-driven clonal hematopoiesis permits colitis-associated tumorigenesis by promoting innate immune tolerance

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Authors

PKPrabhjot KaurAMAnnalisse MckeeJSJixiu Shan

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Overview

Research reveals DNMT3A-driven clonal hematopoiesis enhances tumorigenesis in colitis via immune suppression and macrophage polarization.

Key Points

  • The study investigates how DNMT3A-driven clonal hematopoiesis affects tumor development in colitis.
  • Used a mouse model with mixed bone marrow to study the effects of Dnmt3a mutations on tumor initiation.
  • Induced colitis-associated cancer using azoxymethane and dextran sulfate sodium treatments.
  • Analyzed tumor immune microenvironment and macrophage roles through flow cytometry and scRNA-seq.
  • Profiled cytokine levels in tumor lysates and serum to assess immune responses.
  • Mice with Dnmt3a mutations developed larger tumors in colitis models, indicating enhanced tumorigenesis.
  • Increased infiltration of immune-suppressive M2-like macrophages was observed in the tumor microenvironment.
  • Cytokine profiling showed reduced levels of pro-inflammatory cytokines, indicating immune suppression.
  • Dnmt3a-deficient macrophages exhibited impaired phagocytic activity after inflammatory challenges.

Cite This Study

Kaur et al. (2025) studied this question.

synapsesocial.com/papers/69362f4b4fa91c937236d81ehttps://doi.org/10.1182/blood-2025-3170
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Also Consider

Synapse has enriched 5 closely related papers on similar clinical questions. Consider them for comparative context:

  1. 1Dnmt3a-mutant hematopoietic stem cells generate alloreactive T cells with graft vs host disease and graft vs leukemia effects2025
  2. 2Clonal hematopoiesis drives T cell dysregulation and immune remodeling revealed by GWAS-based mendelian randomization and single-cell transcriptomics2025
  3. 3Single cell multiomic analyses reveal divergent effects of DNMT3A and TET2 mutant clonal hematopoiesis in inflammatory response2024
  4. 4Mesenchymal Stromal Cell Senescence Induced by Dnmt3a-Mutant Hematopoietic Cells is a Targetable Mechanism Driving Clonal Hematopoiesis and Initiation of Hematologic Malignancy2024 · 13 citations
  5. 5Bone marrow environmental alterations underlie proliferative clonal expansion in clonal hematopoiesis2025