ArticleLeukemia2014
Histone deacetylase inhibitors induce apoptosis in myeloid leukemia by suppressing autophagy.
Article in Leukemia, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 68 papers, 2 of them syntheses that pooled it.
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.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
68 citing papers in PubMed, 2 syntheses or guidelines pooled it, 119 citations in OpenAlex.
- Guidelines for the use and interpretation of assays for monitoring autophagy (4th edition)Autophagy · 2021Guideline
- Guidelines for the use and interpretation of assays for monitoring autophagy (3rd edition).Autophagy · 2016Guideline
- Low-dose cytarabine to prevent myeloid leukemia in children with Down syndrome: TMD Prevention 2007 study.Blood advances · 2018Trial
- Transcriptional and epigenetic regulation of autophagy: mechanisms, disease relevance and therapeutic opportunities.Signal transduction and targeted therapy · 2026Review
- Autophagy and Lipid Metabolism as a Therapeutic Target for Overcoming Drug Resistance in Acute Myeloid Leukemia.Life (Basel, Switzerland) · 2026Review
- Perspectives on the origin and therapeutic opportunities in Down syndrome-associated leukemia.Cancer metastasis reviews · 2025Review
- Measurement of Autophagic Activity in Cancer Cells with Flow Cytometric Analysis Using Cyto-ID Staining.Methods in molecular biology (Clifton, N.J.) · 2025Article
- Novel hydroxamic acid derivative induces apoptosis and constrains autophagy in leukemic cells.Journal of advanced research · 2024Article
- Metabolic reprogramming by histone deacetylase inhibition preferentially targets NRF2-activated tumors.Cell reports · 2024Article
- Down syndrome-associated leukaemias: current evidence and challenges.Therapeutic advances in hematology · 2024Review
- Folate-Appended Hydroxypropyl-β-Cyclodextrin Induces Autophagic Cell Death in Acute Myeloid Leukemia Cells.International journal of molecular sciences · 2023Article
- Down syndrome and leukemia: from basic mechanisms to clinical advances.Haematologica · 2023Review
- The inhibition of FKBP5 protects β-cell survival under inflammation stress via AKT/FOXO1 signaling.Cell death discovery · 2023Article
- Expression Changes of SIRT1 and FOXO3a Significantly Correlate with Oxidative Stress Resistance Genes in AML Patients.Indian journal of hematology & blood transfusion : an official journal of Indian Society of Hematology and Blood Transfusion · 2023Article
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- Autolysosomal activation combined with lysosomal destabilization efficiently targets myeloid leukemia cells for cell death.Frontiers in oncology · 2023Article
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- The Question of Survival or Death: What Is the Role of Autophagy in Acute Myeloid Leukemia (AML)?International journal of hematology-oncology and stem cell research · 2022Review
- Detoxified pneumolysin derivative ΔA146Ply inhibits autophagy and induces apoptosis in acute myeloid leukemia cells by activating mTOR signaling.Experimental & molecular medicine · 2022Article
- Review
8 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
15 authors at 4 institutions in 2 countries.
Funding
Abstract
Histone deacetylase (HDAC) inhibitors (HDACis) are well-characterized anti-cancer agents with promising results in clinical trials. However, mechanistically little is known regarding their selectivity in killing malignant cells while sparing normal cells. Gene expression-based chemical genomics identified HDACis as being particularly potent against Down syndrome-associated myeloid leukemia (DS-AMKL) blasts. Investigating the antileukemic function of HDACis revealed their transcriptional and post-translational regulation of key autophagic proteins, including ATG7. This leads to suppression of autophagy, a lysosomal degradation process that can protect cells against damaged or unnecessary organelles and protein aggregates. DS-AMKL cells exhibit low baseline autophagy due to mammalian target of rapamycin (mTOR) activation. Consequently, HDAC inhibition repressed autophagy below a critical threshold, which resulted in accumulation of mitochondria, production of reactive oxygen species, DNA damage and apoptosis. Those HDACi-mediated effects could be reverted upon autophagy activation or aggravated upon further pharmacological or genetic inhibition. Our findings were further extended to other major acute myeloid leukemia subgroups with low basal level autophagy. The constitutive suppression of autophagy due to mTOR activation represents an inherent difference between cancer and normal cells. Thus, via autophagy suppression, HDACis deprive cells of an essential pro-survival mechanism, which translates into an attractive strategy to specifically target cancer cells.
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What OpenQuestion holds
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.