ArticleBritish journal of cancer2023
All-trans retinoic acid enhances the cytotoxic effect of decitabine on myelodysplastic syndromes and acute myeloid leukaemia by activating the RARα-Nrf2 complex.
Article in British journal of cancer, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
What it found
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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.
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Who cites it
21 citing papers in PubMed, 18 citations in OpenAlex.
- Trial
- Decitabine plus all-Haematologica · 2026Trial
- Impact of TP53 Mutation Status in Elderly AML Patients When Adding All-Trans Retinoic Acid or Valproic Acid to Decitabine.European journal of haematology · 2025Trial
- Nucleolin Alterations and ROS Production Associate With Sensitivity of AML Cells to Venetoclax.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2026Article
- Revisiting retinoic acid in AML therapy: mechanisms of action and rational combination strategies.British journal of cancer · 2026Review
- Article
- Genome Agnostic Reprogramming of Acute Myelocytic Leukemia Hallmarks by Targeting Non-Oncogene Addictions with Azacitidine Plus Pioglitazone and All-Trans Retinoic Acid.International journal of molecular sciences · 2026Review
- Self-synergizing mutual prodrug liposomes for targeted cancer therapyTheranostics · 2026Article
- Integrated transcriptomic and methylome analysis reveals retinoic acid pathway activation after decitabine treatment in EBV associated gastric cancer.bioRxiv : the preprint server for biology · 2025Article
- Therapeutic innovations: targeting ROS production in AML with natural and synthetic compounds.Naunyn-Schmiedeberg's archives of pharmacology · 2025Review
- Targeting Nrf2 in acute myeloid leukemia: an updated review on its role in chemoresistance and emerging therapeutic strategies.Medical oncology (Northwood, London, England) · 2025Review
- Targeting epigenetic and post-translational modifications of NRF2: key regulatory factors in disease treatment.Cell death discovery · 2025Review
- The mLeukemia · 2024Article
- Potential of NRF2 Inhibitors-Retinoic Acid, K67, and ML-385-In Overcoming Doxorubicin Resistance in Promyelocytic Leukemia Cells.International journal of molecular sciences · 2024Article
- Role of reactive oxygen species in myelodysplastic syndromes.Cellular & molecular biology letters · 2024Review
- All-trans retinoic acid in hematologic disorders: not just acute promyelocytic leukemia.Frontiers in pharmacology · 2024Review
- Iron overload induces dysplastic erythropoiesis and features of myelodysplasia in Nrf2-deficient mice.Leukemia · 2024Article
- Combined dandelion extract and all-trans retinoic acid induces cytotoxicity in human breast cancer cells.Scientific reports · 2023Article
- Rev-erbα agonist SR9009 protects against cerebral ischemic injury through mechanisms involving Nrf2 pathway.Frontiers in pharmacology · 2023Article
- Targeting chemoresistance and mitochondria-dependent metabolic reprogramming in acute myeloid leukemia.Frontiers in oncology · 2023Review
Corrections and comments
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Authors and funding
27 authors at 3 institutions in 1 country.
Funding
Abstract
backgroundDecitabine (DAC) is used as the first-line therapy in patients with higher-risk myelodysplastic syndromes (HR-MDS) and elderly acute myeloid leukaemia (AML) patients unsuitable for intensive chemotherapy. However, the clinical outcomes of patients treated with DAC as a monotherapy are far from satisfactory. Adding all-trans retinoic acid (ATRA) to DAC reportedly benefitted MDS and elderly AML patients. However, the underlying mechanisms remain unclear and need further explorations from laboratory experiments.
methodsWe used MDS and AML cell lines and primary cells to evaluate the combined effects of DAC and ATRA as well as the underlying mechanisms. We used the MOLM-13-luciferase murine xenograft model to verify the enhanced cytotoxic effect of the drug combination.
resultsThe combination treatment reduced the viability of MDS/AML cells in vitro, delayed leukaemia progress, and extended survival in murine xenograft models compared to non- and mono-drug treated models. DAC application as a single agent induced Nrf2 activation and downstream antioxidative response, and restrained reactive oxygen species (ROS) generation, thus leading to DAC resistance. The addition of ATRA blocked Nrf2 activation by activating the RARα-Nrf2 complex, leading to ROS accumulation and ROS-dependent cytotoxicity.
conclusionsThese results demonstrate that combining DAC and ATRA has potential for the clinical treatment of HR-MDS/AML and merits further exploration.
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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.