ArticleThe Journal of experimental medicine2023
Hematopoietic-specific heterozygous loss of Dnmt3a exacerbates colitis-associated colon cancer.
Article in The Journal of experimental medicine, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
What it found
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The trial behind it
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Who cites it
22 citing papers in PubMed, 25 citations in OpenAlex.
- Clonal Hematopoiesis in Colorectal Cancer: Mechanisms and Implications.Cancer medicine · 2026Review
- Evolution of clonal hematopoiesis during cancer treatment and its impact on outcomes.The Journal of clinical investigation · 2026Article
- Current Understanding of CHIP's Immunobiological Footprint with A Focus on Gastrointestinal Disorders: A Review of the Literature.Current oncology reports · 2026Review
- Clonal hematopoiesis dynamics influences long-term outcomes of follicular lymphoma: Results from FIL FOLL12 trial.HemaSphere · 2026Article
- What's hidden in plain sight? Impact of clonal hematopoiesis on the risk and progression of nonhematologic cancers.Haematologica · 2026Review
- Mutational Signatures and Clonal Hematopoiesis in Intestinal Metaplasia across Countries with Varying Stomach Cancer Incidence.Cancer discovery · 2026Article
- Exploring the Relationship Between Colitis-Associated Cancer and Lipid Metabolism Reprogramming from the Perspective of Inflammation-Cancer Transformation.Journal of inflammation research · 2026Review
- Exosomal miR-29a-3p derived from bone marrow stromal cells suppresses malignant behavior of NSCLC by regulating DNMT3A/JAK2/STAT3 axis.Organogenesis · 2025Article
- Ancestry-dependent patterns of somatic mosaicism and clonal hematopoiesis mutations in over 125,000 individuals reveal distinct cancer associations.Human genomics · 2025Article
- Clonal Hematopoiesis of Indeterminate Potential Influences Breast Cancer Outcomes in a Genotype-Specific Manner.Clinical cancer research : an official journal of the American Association for Cancer Research · 2025Article
- Ageing, immune fitness and cancer.Nature reviews. Cancer · 2025Review
- Clonal hematopoiesis of indeterminate potential: a multisystem hub bridging hematopoietic dysfunction with non-hematopoietic diseases.Military Medical Research · 2025Review
- Clonal Hematopoiesis Dynamics and Evolutionary Fitness During Cancer Treatment Impact Clinical Outcomes.medRxiv : the preprint server for health sciences · 2025Article
- Clonal Hematopoiesis in Cancer and Cardiovascular Disease: JACC: CardioOncology State-of-the-Art Review.JACC. CardioOncology · 2025Review
- Clonal Hematopoiesis and Solid Cancers.Cancer science · 2025Review
- Clonal Hematopoiesis of Indeterminate Potential in Crohn's Disease and Ulcerative Colitis.Inflammatory bowel diseases · 2025Article
- Clonal hematopoiesis in myeloid malignancies and solid tumors.Nature cancer · 2025Review
- Clonal Hematopoiesis: Impact on Health and Disease.Hematological oncology · 2025Review
- Early Detection, Precision Treatment, Recurrence Monitoring: Liquid Biopsy Transforms Colorectal Cancer Therapy.Current cancer drug targets · 2025Review
- Clonal Hematopoiesis of Indeterminate Potential in Crohn's Disease and Ulcerative Colitis.medRxiv : the preprint server for health sciences · 2024Article
Corrections and comments
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Authors and funding
22 authors at 3 institutions in 1 country.
Funding
Abstract
Clonal hematopoiesis (CH) is defined as clonal expansion of mutant hematopoietic stem cells absent diagnosis of a hematologic malignancy. Presence of CH in solid tumor patients, including colon cancer, correlates with shorter survival. We hypothesized that bone marrow-derived cells with heterozygous loss-of-function mutations of DNMT3A, the most common genetic alteration in CH, contribute to the pathogenesis of colon cancer. In a mouse model that combines colitis-associated colon cancer (CAC) with experimental CH driven by Dnmt3a+/Δ, we found higher tumor penetrance and increased tumor burden compared with controls. Histopathological analysis revealed accentuated colonic epithelium injury, dysplasia, and adenocarcinoma formation. Transcriptome profiling of colon tumors identified enrichment of gene signatures associated with carcinogenesis, including angiogenesis. Treatment with the angiogenesis inhibitor axitinib eliminated the colon tumor-promoting effect of experimental CH driven by Dnmt3a haploinsufficiency and rebalanced hematopoiesis. This study provides conceptually novel insights into non-tumor-cell-autonomous effects of hematopoietic alterations on colon carcinogenesis and identifies potential therapeutic strategies.
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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.