Category Ranking
98%
Total Visits
921
Avg Visit Duration
2 minutes
Citations
20
Article Abstract
The fusion oncoprotein CBFβ-SMMHC, expressed in leukemia cases with chromosome 16 inversion, drives leukemia development and maintenance by altering the activity of the transcription factor RUNX1. Here, we demonstrate that CBFβ-SMMHC maintains cell viability by neutralizing RUNX1-mediated repression of MYC expression. Upon pharmacologic inhibition of the CBFβ-SMMHC/RUNX1 interaction, RUNX1 shows increased binding at three MYC distal enhancers, where it represses MYC expression by mediating the replacement of the SWI/SNF complex component BRG1 with the polycomb-repressive complex component RING1B, leading to apoptosis. Combining the CBFβ-SMMHC inhibitor with the BET inhibitor JQ1 eliminates inv(16) leukemia in human cells and a mouse model. Enhancer-interaction analysis indicated that the three enhancers are physically connected with the MYC promoter, and genome-editing analysis demonstrated that they are functionally implicated in deregulation of MYC expression. This study reveals a mechanism whereby CBFβ-SMMHC drives leukemia maintenance and suggests that inhibitors targeting chromatin activity may prove effective in inv(16) leukemia therapy.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6211564 | PMC |
| http://dx.doi.org/10.1016/j.cell.2018.05.048 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Heart failure-specific cardiac fibroblasts contribute to cardiac dysfunction via the MYC-CXCL1-CXCR2 axis.
Nat Cardiovasc Res
September 2025
Department of Cardiology, Keio University School of Medicine, Tokyo, Japan.
Heart failure (HF) is a growing global health issue. While most studies focus on cardiomyocytes, here we highlight the role of cardiac fibroblasts (CFs) in HF. Single-cell RNA sequencing of mouse hearts under pressure overload identified six CF subclusters, with one specific to the HF stage.
View Article and Find Full Text PDFGlobal transcriptional analysis of human FHs 74 Int intestinal epithelial cells after exposure to advanced glycation end products.
PLoS One
September 2025
Institute of Pathophysiology and Allergy Research, Center for Pathophysiology, Infectiology & Immunology, Medical University of Vienna, Vienna, Austria.
Advanced glycation end products (AGEs) and reactive intermediates, such as methylglyoxal, are formed during thermal processing of foods and have been implicated in the pathogenesis of a series of chronic inflammatory diseases. AGEs are thought to directly interact with the intestinal epithelium upon ingestion of thermally processed foods, but their effects on intestinal epithelial cells are poorly understood. This study investigated transcriptomic changes in human intestinal epithelial FHs 74 Int cells after exposure to AGE-modified human serum proteins (AGE-HS), S100A12, a known RAGE ligand, and unmodified human serum proteins (HS).
View Article and Find Full Text PDFAn international prognostic index to predict the early chemoimmunotherapy failure of diffuse large B-cell lymphoma.
Ann Hematol
September 2025
Shanghai Institute of Hematology, State Key Laboratory of Medical Genomics, National Research Center for Translational Medicine at Shanghai, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Approximately 30-40% of diffuse large B-cell lymphoma (DLBCL) patients will develop relapse/refractory disease, who may benefit from novel therapies, such as CAR-T cell therapy. Thus, accurate identification of individuals at high risk of early chemoimmunotherapy failure (ECF) is crucial. Methods.
View Article and Find Full Text PDFAucubin inhibits the activity of lung cancer stem-like cells by targeting degradation of β-catenin.
J Pharm Pharmacol
September 2025
Department of Clinical Pharmacy, Hebei Medical University Third Hospital. No. 139 Ziqiang Road, Qiaoxi District, Shijiazhuang 050051, China.
Objectives: To investigate the antitumor effects of aucubin (AC) in non-small cell lung cancer (NSCLC) and uncover its plausible mechanism against lung cancer stem-like cells (LCSCs).
Methods: In vitro experiments included MTT (3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide, a reagent commonly used for cell viability assay) and colony formation assays to assess anti-proliferative effects on A549 and NCI-H1975 lung cancer cell lines, wound healing and Transwell invasion assays to evaluate inhibition of cell migration and invasion, tumorsphere-formation experiments to detect changes in NSCLC cell stemness, as well as Western blot and quantitative reverse transcription polymerase chain reaction (qRT-PCR) analyses to measure the expression of LCSC markers (CD44, CD133, Oct4, and Nanog). In vivo experiments were conducted to observe the impact of AC on NSCLC metastasis and mouse survival rates.
Integrative network toxicology and molecular docking reveal 4-Nonylphenol's multifaceted mechanisms in breast cancer pathogenesis.
PLoS One
September 2025
Department of Hepatobiliary Surgery, The First Affiliated Hospital of Kunming Medical University, Kunming, Yunnan, China.
Objective: This study employs integrated network toxicology and molecular docking to investigate the molecular basis underlying 4-nonylphenol (4-NP)-mediated enhancement of breast cancer susceptibility.
Methods: We integrated data from multiple databases, including ChEMBL, STITCH, Swiss Target Prediction, GeneCards, OMIM and TTD. Core compound-disease-associated target genes were identified through Protein-Protein Interaction (PPI) network analysis.