ArticleJournal of the National Cancer Institute2008
Identification of chromatin remodeling genes Arid4a and Arid4b as leukemia suppressor genes.
Article in Journal of the National Cancer Institute, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 56 papers, 1 of them a synthesis that pooled it.
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Who cites it
56 citing papers in PubMed, 1 synthesis or guideline pooled it, 84 citations in OpenAlex.
- The Coming of Age of Preclinical Models of MDS.Frontiers in oncology · 2022Pooled it
- Pediatric T-cell lymphoblastic leukemia evolves into relapse by clonal selection, acquisition of mutations and promoter hypomethylation.Haematologica · 2015Trial
- FM-GPT: Bayesian fine mapping for phenome-wide transcriptome-wide association studies.PLoS genetics · 2026Article
- FM-GPT: Bayesian fine mapping for phenome-wide transcriptome-wide association studies.bioRxiv : the preprint server for biology · 2026Article
- EpGAT: integrating epigenetics and 3D genome structure to predict alternative splicing and polyadenylation.Briefings in bioinformatics · 2026Article
- HOXB5 in precision oncology: regulatory networks, functional duality, and clinical prospects.Journal of translational medicine · 2026Review
- Review
- ARID4B Promotes the Progression of Hepatocellular Carcinoma Through the PI3K/AKT Pathway.Annals of surgical oncology · 2025Article
- Arid4a Suppresses Breast Tumor Metastasis by Enhancing MTSS1 Expression via mRNA Stability.Cancer medicine · 2025Article
- Machine learning selection of basement membrane-associated genes and development of a predictive model for kidney fibrosis.Scientific reports · 2025Article
- Retinol-binding protein type 1 expression predicts poor prognosis in head and neck squamous cell carcinoma.BMC cancer · 2024Article
- Comprehensive Atlas of Alternative Splicing Reveals NSRP1 Promoting Adipogenesis throughInternational journal of molecular sciences · 2024Article
- Quantitative association between gene expression and blood cell production of individual hematopoietic stem cells in mice.Science advances · 2024Article
- Epigenetic regulation of human FOXP3+ Tregs: from homeostasis maintenance to pathogen defense.Frontiers in immunology · 2024Review
- Heterozygous Knockout ofGenes · 2023Article
- Bone marrow-confined IL-6 signaling mediates the progression of myelodysplastic syndromes to acute myeloid leukemia.The Journal of clinical investigation · 2022Article
- A novel heterozygous missense variant of the ARID4A gene identified in Han Chinese families with schizophrenia-diagnosed siblings that interferes with DNA-binding activity.Molecular psychiatry · 2022Article
- Epigenome-wide analysis of long-term air pollution exposure and DNA methylation in monocytes: results from the Multi-Ethnic Study of Atherosclerosis.Epigenetics · 2022Article
- Positive Selection and Enhancer Evolution Shaped Lifespan and Body Mass in Great Apes.Molecular biology and evolution · 2022Article
- Differentiation of fetal hematopoietic stem cells requires ARID4B to restrict autocrine KITLG/KIT-Src signaling.Cell reports · 2021Article
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
backgroundLeukemia evolves through a multistep process from premalignancy to malignancy. Epigenetic alterations, including histone modifications, have been proposed to play an important role in tumorigenesis. The involvement of two chromatin remodeling genes, retinoblastoma-binding protein 1 (Rbbp1/Arid4a) and Rbbp1-like 1 (Rbbp1l1/Arid4b), in leukemogenesis was not characterized.
methodsThe leukemic phenotype of mice deficient for Arid4a with or without haploinsufficiency for Arid4b was investigated by serially monitoring complete blood counts together with microscopic histologic analysis and flow cytometric analysis of bone marrow and spleen from the Arid4a(-/-) mice or Arid4a(-/-)Arid4b(+/-) mice. Regulation in bone marrow cells of downstream genes important for normal hematopoiesis was analyzed by reverse transcription-polymerase chain reaction. Genotypic effects on histone modifications were examined by western blotting and immunofluorescence analysis. All statistical tests were two-sided.
resultsYoung (2-5 months old) Arid4a-deficient mice had ineffective blood cell production in all hematopoietic lineages. Beyond 5 months of age, the Arid4a(-/-) mice manifested monocytosis, accompanied by severe anemia and thrombocytopenia. These sick Arid4a(-/-) mice showed bone marrow failure with myelofibrosis associated with splenomegaly and hepatomegaly. Five of 42 Arid4a(-/-) mice and 10 of 12 Arid4a(-/-)Arid4b(+/-) mice progressed to acute myeloid leukemia (AML) and had rapid further increases of leukocyte counts. Expression of Hox genes (Hoxb3, Hoxb5, Hoxb6, and Hoxb8) was decreased in Arid4a-deficient bone marrow cells with or without Arid4b haploinsufficiency, and FoxP3 expression was reduced in Arid4a(-/-)Arid4b(+/-) bone marrow. Increases of histone trimethylation of H3K4, H3K9, and H4K20 (fold increases in trimethylation = 32, 95% confidence interval [CI] = 27 to 32; 45, 95% CI = 41 to 49; and 2.2, 95% CI = 1.7 to 2.7, respectively) were observed in the bone marrow of Arid4a-deficient mice.
conclusionsArid4a-deficient mice initially display ineffective hematopoiesis, followed by transition to chronic myelomonocytic leukemia (CMML)-like myelodysplastic/myeloproliferative disorder, and then transformation to AML. The disease processes in the Arid4a-deficient mice are very similar to the course of events in humans with CMML and AML. This mouse model has the potential to furnish additional insights into the role of epigenetic alterations in leukemogenesis, and it may be useful in developing novel pharmacological approaches to treatment of preleukemic and leukemic states.
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