ArticleSignal transduction and targeted therapy2021
CREBBP/EP300 mutations promoted tumor progression in diffuse large B-cell lymphoma through altering tumor-associated macrophage polarization via FBXW7-NOTCH-CCL2/CSF1 axis.
Article in Signal transduction and targeted therapy, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 139 papers.
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Who cites it
139 citing papers in PubMed, 224 citations in OpenAlex.
- Chidamide, a Histone Deacetylase Inhibitor, Combined With R-GemOx in Relapsed/Refractory Diffuse Large B-Cell Lymphoma (TRUST): A Multicenter, Single-Arm, Phase 2 Trial.Cancer medicine · 2025Trial
- Dysregulated KMT2D mutant targeting immunogenic rewiring to overcome epigenetic entropy promotes follicular lymphomagenesis.Experimental hematology & oncology · 2026Article
- Review
- Oncogenic Mutations and Tumor Microenvironment Alterations in Diffuse Large B-Cell Lymphoma With Bulky Disease.Cancer medicine · 2026Article
- Inhibition of the EP300/Notch Signaling Pathway Regulates Proliferation and Apoptosis in Oral Squamous Cell Carcinoma.Journal of oral pathology & medicine : official publication of the International Association of Oral Pathologists and the American Academy of Oral Pathology · 2026Article
- FBXW7 Inhibited M2 Macrophage Polarization in Endometrial Cancer by Reducing CCL2 Secretion Through Ubiquitination of MYBL2 Subtitle: The Role of FBXW7 on M2 Macrophage Polarization in EC.Biochemical genetics · 2026Article
- Pretreatment With BTK Inhibitors Improved the Sensitivity of DLBCL Cells to CAR-T Cells in a Coculture System by Downregulating the Polarisation of M2 Macrophages.Journal of cellular and molecular medicine · 2026Article
- Article
- TBL1XR1 mutations promoted tumor progression in diffuse large B-cell lymphoma through impairing nature killer cytotoxicity via the MYC-CD47/PD-L1 axis.Molecular cancer · 2026Article
- Molecular Mechanisms of Diffuse Large B-Cell Lymphoma and the Complexities of Tumor Development.Saudi medical journal · 2026Review
- PCGF1-mediated bivalent promoter remodeling enables NK cell immune evasion in non-small cell lung cancer.Cell death & disease · 2026Article
- Molecular Insights and Novel Therapies for Lymphoproliferative Disorders.International journal of molecular sciences · 2026Review
- Molecular Mechanisms of Resistance to Bispecific Antibodies in Diffuse Large B-Cell Lymphoma.Cells · 2026Review
- Chronic lymphocytic leukemia with IGH/BCL2 fusion and clonal heterogeneity: phenotypic and molecular profiling analysis of a rare case.Annals of hematology · 2026Article
- Clinical characterization and targeted genetic mutation profiling of autoimmune disease-associated B-cell lymphoma.Discover oncology · 2026Article
- Notch signaling in the tumor microenvironment: recent advances and targeted therapeutics.Molecular cancer · 2026Review
- Integrated analysis of the blood metallome and DNA methylation, gene expression, and protein levels of immune-associated genes in residents from mining region.Environmental geochemistry and health · 2026Article
- Protein acetylation in atherosclerosis: beyond inflammation to core cellular processes and therapeutic potential.Frontiers in immunology · 2026Review
- Tumor Microenvironment Onmyoji: Cytokines with Dual Protumor and Antitumor Roles.Cancer communications (London, England) · 2026Review
- JMJD3 regulates the M2-like macrophage polarization and promotes the growth of breast cancer cells via STAT6/IRF4 axis.PloS one · 2026Article
79 more citing papers are in PubMed but not listed here.
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Authors and funding
12 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Epigenetic alterations play an important role in tumor progression of diffuse large B-cell lymphoma (DLBCL). However, the biological relevance of epigenetic gene mutations on tumor microenvironment remains to be determined. The core set of genes relating to histone methylation (KMT2D, KMT2C, EZH2), histone acetylation (CREBBP, EP300), DNA methylation (TET2), and chromatin remodeling (ARID1A) were detected in the training cohort of 316 patients by whole-genome/exome sequencing (WGS/WES) and in the validation cohort of 303 patients with newly diagnosed DLBCL by targeted sequencing. Their correlation with peripheral blood immune cells and clinical outcomes were assessed. Underlying mechanisms on tumor microenvironment were investigated both in vitro and in vivo. Among all 619 DLBCL patients, somatic mutations in KMT2D (19.5%) were most frequently observed, followed by mutations in ARID1A (8.7%), CREBBP (8.4%), KMT2C (8.2%), TET2 (7.8%), EP300 (6.8%), and EZH2 (2.9%). Among them, CREBBP/EP300 mutations were significantly associated with decreased peripheral blood absolute lymphocyte-to-monocyte ratios, as well as inferior progression-free and overall survival. In B-lymphoma cells, the mutation or knockdown of CREBBP or EP300 inhibited H3K27 acetylation, downregulated FBXW7 expression, activated the NOTCH pathway, and downstream CCL2/CSF1 expression, resulting in tumor-associated macrophage polarization to M2 phenotype and tumor cell proliferation. In B-lymphoma murine models, xenografted tumors bearing CREBBP/EP300 mutation presented lower H3K27 acetylation, higher M2 macrophage recruitment, and more rapid tumor growth than those with CREBBP/EP300 wild-type control via FBXW7-NOTCH-CCL2/CSF1 axis. Our work thus contributed to the understanding of aberrant histone acetylation regulation on tumor microenvironment as an alternative mechanism of tumor progression in DLBCL.
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