ArticleCell death & disease2018
Arsenic trioxide promoting ETosis in acute promyelocytic leukemia through mTOR-regulated autophagy.
Article in Cell death & disease, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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Who cites it
25 citing papers in PubMed, 45 citations in OpenAlex.
- Inflammation and RONS Dysregulation by Redox Enzymes as Mechanistic Links in HIV-1-Cancer Comorbidity.Pathogens (Basel, Switzerland) · 2026Review
- Venetoclax induces mitochondrial apoptosis and autophagy to overcome arsenic trioxide resistance in acute promyelocytic leukemia.Journal of translational medicine · 2026Article
- Long-term Remission in a Case of Acute Promyelocytic Leukaemia with Coexistent t(15;17) and t(8;21) Without Chemotherapy.Indian journal of hematology & blood transfusion : an official journal of Indian Society of Hematology and Blood Transfusion · 2025Article
- The inducible role of autophagy in cell death: emerging evidence and future perspectives.Cell communication and signaling : CCS · 2025Review
- Resveratrol decreases extracellular traps (ETs) in acute promyelocytic leukemia (NB4) cells.PloS one · 2025Article
- NETs - as predictors and targets of supportive therapy for cancer treatment.Frontiers in immunology · 2025Review
- Hepatotoxicity induced by arsenic trioxide: clinical features, mechanisms, preventive and potential therapeutic strategies.Frontiers in pharmacology · 2025Review
- Hemorrhage in acute promyelocytic leukemia-fibrinolysis in focus.Research and practice in thrombosis and haemostasis · 2024Review
- Arsenic trioxide: applications, mechanisms of action, toxicity and rescue strategies to date.Archives of pharmacal research · 2024Review
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- Mechanistic update of Trisenox in blood cancer.Current research in pharmacology and drug discovery · 2023Review
- The dual role of autophagy in acute myeloid leukemia.Journal of hematology & oncology · 2022Review
- Metabolic adaptation drives arsenic trioxide resistance in acute promyelocytic leukemia.Blood advances · 2022Article
- Immunoregulation and clinical significance of neutrophils/NETs-ANGPT2 in tumor microenvironment of gastric cancer.Frontiers in immunology · 2022Article
- Extracellular Traps Increase Burden of Bleeding by Damaging Endothelial Cell in Acute Promyelocytic Leukaemia.Frontiers in immunology · 2022Article
- Neutrophil extracellular traps: New players in cancer research.Frontiers in immunology · 2022Review
- Honokiol induces paraptosis-like cell death of acute promyelocytic leukemia via mTOR & MAPK signaling pathways activation.Apoptosis : an international journal on programmed cell death · 2021Article
- Endothelial damage and a thin intercellular fibrin network promote haemorrhage in acute promyelocytic leukaemia.EBioMedicine · 2020Article
- Arsenic trioxide induces autophagic degradation of the FLT3-ITD mutated protein in FLT3-ITD acute myeloid leukemia cells.Journal of Cancer · 2020Article
Corrections and comments
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Authors and funding
16 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Despite the high efficacy and safety of arsenic trioxide (ATO) in treating acute promyelocytic leukemia (APL) and eradicating APL leukemia-initiating cells (LICs), the mechanism underlying its selective cytotoxicity remains elusive. We have recently demonstrated that APL cells undergo a novel cell death program, termed ETosis, through autophagy. However, the role of ETosis in ATO-induced APL LIC eradication remains unclear. For this study, we evaluated the effects of ATO on ETosis and the contributions of drug-induced ETosis to APL LIC eradication. In NB4 cells, ATO primarily increased ETosis at moderate concentrations (0.5-0.75 μM) and stimulated apoptosis at higher doses (1.0-2.0 μM). Furthermore, ATO induced ETosis through mammalian target of rapamycin (mTOR)-dependent autophagy, which was partially regulated by reactive oxygen species. Additionally, rapamycin-enhanced ATO-induced ETosis in NB4 cells and APL cells from newly diagnosed and relapsed patients. In contrast, rapamycin had no effect on apoptosis in these cells. We also noted that PML/RARA oncoprotein was effectively cleared with this combination. Intriguingly, activation of autophagy with rapamycin-enhanced APL LIC eradication clearance by ATO in vitro and in a xenograft APL model, while inhibition of autophagy spared clonogenic cells. Our current results show that ATO exerts antileukemic effects at least partially through ETosis and targets LICs primarily through ETosis. Addition of drugs that target the ETotic pathway could be a promising therapeutic strategy to further eradicate LICs and reduce relapse.
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