ArticleLeukemia2019
The acetyltransferase GCN5 maintains ATRA-resistance in non-APL AML.
Article in Leukemia, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 21 papers.
What it found
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Who cites it
21 citing papers in PubMed, 42 citations in OpenAlex.
- Dynamic regulation of H3K9 modifications in cancer: pathogenesis and targeted therapies.Biomarker research · 2026Review
- Revisiting retinoic acid in AML therapy: mechanisms of action and rational combination strategies.British journal of cancer · 2026Review
- Article
- mTOR inhibition promotes ATRA-induced cancer cell differentiation by overcoming a metabolic hyperactive state.Journal of translational medicine · 2026Article
- Synergistic potential of CDK4/6 inhibitors and ATRA in non-APL AML.British journal of haematology · 2025Article
- Targeting the lncRNA RBM5-AS1/GCN5 axis under fasting conditions reprograms Glycolysis and induces apoptosis in ovarian cancer cells.Molecular biology reports · 2025Article
- The histone modifier KAT2A presents a selective target in a subset of well-differentiated microsatellite-stable colorectal cancers.Cell death and differentiation · 2025Article
- Targeting epigenetic regulators to overcome drug resistance in the emerging human fungal pathogen Candida auris.Nature communications · 2025Article
- GlycoRNA-rich, neutrophil membrane-coated, siMT1-loaded nanoparticles mitigate abdominal aortic aneurysm progression by inhibiting the formation of neutrophil extracellular traps.Materials today. Bio · 2025Article
- All-trans retinoic acid in hematologic disorders: not just acute promyelocytic leukemia.Frontiers in pharmacology · 2024Review
- Dual inhibition of EZH2 and G9A/GLP histone methyltransferases by HKMTI-1-005 promotes differentiation of acute myeloid leukemia cells.Frontiers in cell and developmental biology · 2023Article
- Targeted Epigenetic Interventions in Cancer with an Emphasis on Pediatric Malignancies.Biomolecules · 2022Review
- Noncanonical EZH2 drives retinoic acid resistance of variant acute promyelocytic leukemias.Blood · 2022Article
- Co-Formulation of Amphiphilic Cationic and Anionic Cyclodextrins Forming Nanoparticles for siRNA Delivery in the Treatment of Acute Myeloid Leukaemia.International journal of molecular sciences · 2022Article
- Article
- Complex functions of Gcn5 and Pcaf in development and disease.Biochimica et biophysica acta. Gene regulatory mechanisms · 2021Review
- IGFBP7 activates retinoid acid-induced responses in acute myeloid leukemia stem and progenitor cells.Blood advances · 2020Article
- Review
- Dissecting the novel partners of nuclear c-Raf and its role in all-trans retinoic acid (ATRA)-induced myeloblastic leukemia cells differentiation.Experimental cell research · 2020Article
- The transcriptional corepressor CBFA2T3 inhibits all-The Journal of biological chemistry · 2020Article
Corrections and comments
- Erratum issued
Authors and funding
20 authors at 7 institutions in 6 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
To date, only one subtype of acute myeloid leukemia (AML), acute promyelocytic leukemia (APL) can be effectively treated by differentiation therapy utilizing all-trans retinoic acid (ATRA). Non-APL AMLs are resistant to ATRA. Here we demonstrate that the acetyltransferase GCN5 contributes to ATRA resistance in non-APL AML via aberrant acetylation of histone 3 lysine 9 (H3K9ac) residues maintaining the expression of stemness and leukemia associated genes. We show that inhibition of GCN5 unlocks an ATRA-driven therapeutic response. This response is potentiated by coinhibition of the lysine demethylase LSD1, leading to differentiation in most non-APL AML. Induction of differentiation was not correlated to a specific AML subtype, cytogenetic, or mutational status. Our study shows a previously uncharacterized role of GCN5 in maintaining the immature state of leukemic blasts and identifies GCN5 as a therapeutic target in AML. The high efficacy of the combined epigenetic treatment with GCN5 and LSD1 inhibitors may enable the use of ATRA for differentiation therapy of non-APL AML. Furthermore, it supports a strategy of combined targeting of epigenetic factors to improve treatment, a concept potentially applicable for a broad range of malignancies.
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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.