ArticleLeukemia2019
Combination treatment of acute myeloid leukemia cells with DNMT and HDAC inhibitors: predominant synergistic gene downregulation associated with gene body demethylation.
Article in Leukemia, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 61 papers.
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Who cites it
61 citing papers in PubMed, 120 citations in OpenAlex.
- The antileukemic activity of decitabine upon PML/RARA-negative AML blasts is supported by all-trans retinoic acid: in vitro and in vivo evidence for cooperation.Blood cancer journal · 2022Trial
- Epigenetic deciphering of ovarian aging: multilayer interactive mechanisms and targeted reversal strategies.Epigenetics & chromatin · 2026Review
- DNMT inhibitor ameliorates hyperglycemia and renal inflammation partially via reversing hypermethylation-induced Klotho suppression in diabetic mice.Clinical epigenetics · 2026Article
- Histone deacetylases: Function in tumor development and therapeutic prospects (Review).Oncology letters · 2026Review
- Myelodysplasia From Valproic Acid Resolved by Cessation.Case reports in hematology · 2026Article
- Mechanotransduction-Epigenetic Coupling in Pulmonary Regeneration: Multifunctional Bioscaffolds as Emerging Tools.Pharmaceuticals (Basel, Switzerland) · 2025Review
- Epigenetic agents, zebularine and valproic acid, inhibit the growth of the oral squamous cell carcinoma cell line HSC4 in vitro and in vivo.Discover oncology · 2025Article
- Article
- Stochastic demethylation and redundant epigenetic suppressive mechanisms generate highly heterogeneous responses to pharmacological DNA methyltransferase inhibition.Journal of experimental & clinical cancer research : CR · 2025Article
- Valproic Acid Enhances Venetoclax Efficacy in Targeting Acute Myeloid Leukemia.Diseases (Basel, Switzerland) · 2025Article
- Mapping epigenetic modifications by sequencing technologies.Cell death and differentiation · 2025Review
- FOXN3-AS1: A Candidate Prognostic Marker and Epigenetic Target with Immunotherapeutic Implications in Acute Myeloid Leukemia.Current medicinal chemistry · 2025Article
- Targeting the epigenome with advanced delivery strategies for epigenetic modulators.Bioengineering & translational medicine · 2025Review
- Epigenetic and metabolic reprogramming via nanotechnology: a synergistic approach to cancer vaccination in lung tumors.Frontiers in genetics · 2025Review
- DNA methylation and immune evasion in triple-negative breast cancer: challenges and therapeutic opportunities.Frontiers in oncology · 2025Review
- Histone deacetylase inhibitors for leukemia treatment: current status and future directions.European journal of medical research · 2024Review
- The Wnt-pathway corepressor TLE3 interacts with the histone methyltransferase KMT1A to inhibit differentiation in Rhabdomyosarcoma.Oncogene · 2024Article
- Emerging roles of MITF as a crucial regulator of immunity.Experimental & molecular medicine · 2024Review
- HDAC-driven mechanisms in anticancer resistance: epigenetics and beyond.Cancer drug resistance (Alhambra, Calif.) · 2024Review
- Systematic characterization of the HOXA9 downstream targets in MLL-r leukemia by noncoding CRISPR screens.Nature communications · 2023Article
1 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
9 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
DNA methyltransferase inhibitors (DNMTi) approved for older AML patients are clinically tested in combination with histone deacetylase inhibitors (HDACi). The mechanism of action of these drugs is still under debate. In colon cancer cells, 5-aza-2'-deoxycytidine (DAC) can downregulate oncogenes and metabolic genes by reversing gene body DNA methylation, thus implicating gene body methylation as a novel drug target. We asked whether DAC-induced gene body demethylation in AML cells is also associated with gene repression, and whether the latter is enhanced by HDACi.Transcriptome analyses revealed that a combined treatment with DAC and the HDACi panobinostat or valproic acid affected significantly more transcripts than the sum of the genes regulated by either treatment alone, demonstrating a quantitative synergistic effect on genome-wide expression in U937 cells. This effect was particularly striking for downregulated genes. Integrative methylome and transcriptome analyses showed that a massive downregulation of genes, including oncogenes (e.g., MYC) and epigenetic modifiers (e.g., KDM2B, SUV39H1) often overexpressed in cancer, was associated predominantly with gene body DNA demethylation and changes in acH3K9/27. These findings have implications for the mechanism of action of combined epigenetic treatments, and for a better understanding of responses in trials where this approach is clinically tested.
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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.