ArticleCancer research2011
6-Thioguanine reactivates epigenetically silenced genes in acute lymphoblastic leukemia cells by facilitating proteasome-mediated degradation of DNMT1.
Article in Cancer research, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
What it found
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Who cites it
26 citing papers in PubMed, 50 citations in OpenAlex.
- 6-thioguanine inhibits EV71 replication by reducing BIRC3-mediated autophagy.BMC microbiology · 2025Article
- Epigenetic regulation of the respiratory chain by a mitochondrial distress-related redox signal.Frontiers in cell and developmental biology · 2025Article
- miRNAs as predictive biomarkers of response to treatment in pediatric patients with acute lymphoblastic leukemia.Oncology letters · 2024Article
- Polymer-Based Nanoparticles as Drug Delivery Systems for Purines of Established Importance in Medicine.Nanomaterials (Basel, Switzerland) · 2023Review
- Review
- 6-Thioguanine Inhibits Herpes Simplex Virus 1 Infection of Eyes.Microbiology spectrum · 2021Article
- Genome-wide DNA methylome analysis identifies methylation signatures associated with survival and drug resistance of ovarian cancers.Clinical epigenetics · 2021Article
- Combined epigenetic and metabolic treatments overcome differentiation blockade in acute myeloid leukemia.iScience · 2021Article
- The regulatory effect of 6-TG on lncRNA-miRNA-mRNA ceRNA network in triple-negative breast cancer cell line.Bioscience reports · 2021Article
- Activation of SIRT6 by DNA hypomethylating agents and clinical consequences on combination therapy in leukemia.Scientific reports · 2020Article
- Transcriptomics Analysis of the Tumor-Inhibitory Pathways of 6-Thioguanine in MCF-7 Cells via Silencing DNMT1 Activity.OncoTargets and therapy · 2020Article
- Thioguanine Induces Apoptosis in Triple-Negative Breast Cancer by Regulating PI3K-AKT Pathway.Frontiers in oncology · 2020Article
- Recent Advances in the Targeting of Epigenetic Regulators in B-Cell Non-Hodgkin Lymphoma.Frontiers in genetics · 2019Review
- Thymoquinone-Induced Reactivation of Tumor Suppressor Genes in Cancer Cells Involves Epigenetic Mechanisms.Epigenetics insights · 2019Article
- Microbiome-Epigenome Interactions and the Environmental Origins of Inflammatory Bowel Diseases.Journal of pediatric gastroenterology and nutrition · 2016Review
- The role of aberrant proteolysis in lymphomagenesis.Current opinion in hematology · 2015Review
- 6-Thioguanine and zebularine down-regulate DNMT1 and globally demethylate canine malignant lymphoid cells.BMC veterinary research · 2014Article
- Comprehensive characterization of (S)GTP-binding proteins by orthogonal quantitative (S)GTP-affinity profiling and (S)GTP/GTP competition assays.Analytical chemistry · 2014Article
- Fludarabine downregulates indoleamine 2,3-dioxygenase in tumors via a proteasome-mediated degradation mechanism.PloS one · 2014Article
- Quantitative assessment of Tet-induced oxidation products of 5-methylcytosine in cellular and tissue DNA.Nucleic acids research · 2013Article
Corrections and comments
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Authors and funding
9 authors at 4 institutions in 2 countries.
Funding
Abstract
Thiopurines including 6-thioguanine ((S)G), 6-mercaptopurine, and azathioprine are effective anticancer agents with remarkable success in clinical practice, especially in effective treatment of acute lymphoblastic leukemia (ALL). (S)G is understood to act as a DNA hypomethylating agent in ALL cells, however, the underlying mechanism leading to global cytosine demethylation remains unclear. Here we report that (S)G treatment results in reactivation of epigenetically silenced genes in T leukemia cells. Bisulfite genomic sequencing revealed that (S)G treatment universally elicited demethylation in the promoters and/or first exons of the genes that were reactivated. (S)G treatment also attenuated the expression of histone lysine-specific demethylase 1 (LSD1), thereby stimulating lysine methylation of the DNA methylase DNMT1 and triggering its degradation via the ubiquitin-proteasomal pathway. Taken together, our findings reveal a previously uncharacterized but vital mechanistic link between (S)G treatment and DNA hypomethylation.
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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.