ArticleLeukemia2017
Targeting HDAC3, a new partner protein of AKT in the reversal of chemoresistance in acute myeloid leukemia via DNA damage response.
Article in Leukemia, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 46 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
46 citing papers in PubMed, 75 citations in OpenAlex.
- An AI-Assisted Workflow for Rapid Prioritization of FDA-Approved Drugs as HDAC3 Inhibitor Candidates for Drug Repurposing.Biology · 2026Article
- Dual SYK-HDAC Inhibitor Elicits Striking Efficacy against Acute Myeloid Leukemia: Rational Design, Synthesis, and Biological Evaluation.Journal of medicinal chemistry · 2026Article
- Epigenetic modifications in cancer drug resistance: molecular mechanisms and therapeutic interventions.Molecular biomedicine · 2026Review
- HDAC inhibitors in cancer therapy: sensitization mechanisms, combination strategies, and translational challenges.Frontiers in cell and developmental biology · 2026Review
- Chidamide enhances the sensitivity of gastric cancer to 5-fluorouracil chemotherapy by suppressing the HDAC3/HNF4A/TYMS axis.Cell death & disease · 2025Article
- Article
- Zinc Finger Protein 82 regulates p53 protein stability through histone deacetylase and enhances neo-adjuvant chemotherapy in esophageal cancer.Cell death & disease · 2025Article
- Investigating the binding mechanism of AML inhibitors based on panobinostat with HDAC3 proteins using Gaussian accelerated molecular dynamics.RSC advances · 2025Article
- CD37 regulates the self-renewal of leukemic stem cells via integrin-mediated signaling in acute myeloid leukemia.Stem cell reports · 2025Article
- Review
- The role of acetylation and deacetylation in cancer metabolism.Clinical and translational medicine · 2025Review
- Novel hydroxamic acid derivative induces apoptosis and constrains autophagy in leukemic cells.Journal of advanced research · 2024Article
- Article
- HDAC-driven mechanisms in anticancer resistance: epigenetics and beyond.Cancer drug resistance (Alhambra, Calif.) · 2024Review
- [Chidamide inhibits proliferation and promotes apoptosis of esophageal squamous cell carcinoma cells by inhibiting the PI3K/Akt and ERK1/2 pathways and increasing DNA damage].Nan fang yi ke da xue xue bao = Journal of Southern Medical University · 2023Article
- HDAC11 mediates the ubiquitin-dependent degradation of p53 and inhibits the anti-leukemia effect of PD0166285.Medical oncology (Northwood, London, England) · 2023Article
- Post-translational modification of CDK1-STAT3 signaling by fisetin suppresses pancreatic cancer stem cell properties.Cell & bioscience · 2023Article
- The NCOR-HDAC3 co-repressive complex modulates the leukemogenic potential of the transcription factor ERG.Nature communications · 2023Article
- Disruption of mitochondrial oxidative phosphorylation by chidamide eradicates leukemic cells in AML.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2023Article
- Targeting HDAC3 to overcome the resistance to ATRA or arsenic in acute promyelocytic leukemia through ubiquitination and degradation of PML-RARα.Cell death and differentiation · 2023Article
Corrections and comments
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Authors and funding
14 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Resistance to cytotoxic chemotherapy drugs remains as the major cause of treatment failure in acute myeloid leukemia. Histone deacetylases (HDAC) are important regulators to maintain chromatin structure and control DNA damage; nevertheless, how each HDAC regulates genome stability remains unclear, especially under genome stress conditions. Here, we identified a mechanism by which HDAC3 regulates DNA damage repair and mediates resistance to chemotherapy drugs. In addition to inducing DNA damage, chemotherapy drugs trigger upregulation of HDAC3 expression in leukemia cells. Using genetic and pharmacological approaches, we show that HDAC3 contributes to chemotherapy resistance by regulating the activation of AKT, a well-documented factor in drug resistance development. HDAC3 binds to AKT and deacetylates it at the site Lys20, thereby promoting the phosphorylation of AKT. Chemotherapy drug exposure enhances the interaction between HDAC3 and AKT, resulting in decrease in AKT acetylation and increase in AKT phosphorylation. Whereas HDAC3 depletion or inhibition abrogates these responses and meanwhile sensitizes leukemia cells to chemotoxicity-induced apoptosis. Importantly, in vivo HDAC3 suppression reduces leukemia progression and sensitizes MLL-AF9
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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.