ArticleThe Journal of clinical investigation2010
Induction of autophagy-dependent necroptosis is required for childhood acute lymphoblastic leukemia cells to overcome glucocorticoid resistance.
Article in The Journal of clinical investigation, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 167 papers, 3 of them syntheses that pooled it.
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Who cites it
167 citing papers in PubMed, 3 syntheses or guidelines pooled it, 311 citations in OpenAlex.
- Guidelines for the use and interpretation of assays for monitoring autophagy (4th edition)Autophagy · 2021Guideline
- Targeting autophagy for combating chemoresistance and radioresistance in glioblastoma.Apoptosis : an international journal on programmed cell death · 2018Pooled it
- Guidelines for the use and interpretation of assays for monitoring autophagy (3rd edition).Autophagy · 2016Guideline
- Targeting autophagy and metabolism for ewing sarcoma.Molecular biology reports · 2025Review
- Loss of ADAM15 prevents necroptosis induction by partial RIPK1 degradation due to enhanced TNF-R1 surface expression and basal caspase-8 activation.Cell communication and signaling : CCS · 2025Article
- The crosstalk between MiRNAs and autophagy in leukemia: mechanisms and therapeutic insights.Discover oncology · 2025Review
- Liquid Plasma Induces Necroptosis Without Inflammatory Responses in Head and Neck Cancer Cells.World journal of oncology · 2025Article
- The inducible role of autophagy in cell death: emerging evidence and future perspectives.Cell communication and signaling : CCS · 2025Review
- A Bibliometric Analysis of Drug Resistance in Pediatric Acute Lymphoblastic Leukemia.Advanced biomedical research · 2025Article
- The Interplay Between Autophagy and Regulated Necrosis.Antioxidants & redox signaling · 2023Review
- Dexamethasone-Induced Fatty Acid Oxidation and Autophagy/Mitophagy Are Essential for T-ALL Glucocorticoid Resistance.Cancers · 2023Article
- Microphysiological Drug-Testing Platform for Identifying Responses to Prodrug Treatment in Primary Leukemia.Advanced healthcare materials · 2023Article
- Chronic oligodendrocyte injury in central nervous system pathologies.Communications biology · 2022Review
- Autophagy in Hematological Malignancies.Cancers · 2022Review
- Construction of a novel signature and prediction of the immune landscape in gastric cancer based on necroptosis-related genes.Scientific reports · 2022Article
- Molecular Mechanisms of Autophagy in Cancer Development, Progression, and Therapy.Biomedicines · 2022Review
- Induction of autophagy-dependent ferroptosis to eliminate drug-tolerant human retinoblastoma cells.Cell death & disease · 2022Article
- Pan-Caspase Inhibitor zVAD Induces Necroptotic and Autophagic Cell Death in TLR3/4-Stimulated Macrophages.Molecules and cells · 2022Article
- A Novel Prognostic Signature Associated with Immunotherapeutic Response for Hepatocellular Carcinoma.Frontiers in surgery · 2022Article
- Understanding the Role of Autophagy in Cancer Formation and Progression Is a Real Opportunity to Treat and Cure Human Cancers.Cancers · 2021Review
107 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
10 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
In vivo resistance to first-line chemotherapy, including to glucocorticoids, is a strong predictor of poor outcome in children with acute lymphoblastic leukemia (ALL). Modulation of cell death regulators represents an attractive strategy for subverting such drug resistance. Here we report complete resensitization of multidrug-resistant childhood ALL cells to glucocorticoids and other cytotoxic agents with subcytotoxic concentrations of obatoclax, a putative antagonist of BCL-2 family members. The reversal of glucocorticoid resistance occurred through rapid activation of autophagy-dependent necroptosis, which bypassed the block in mitochondrial apoptosis. This effect was associated with dissociation of the autophagy inducer beclin-1 from the antiapoptotic BCL-2 family member myeloid cell leukemia sequence 1 (MCL-1) and with a marked decrease in mammalian target of rapamycin (mTOR) activity. Consistent with a protective role for mTOR in glucocorticoid resistance in childhood ALL, combination of rapamycin with the glucocorticoid dexamethasone triggered autophagy-dependent cell death, with characteristic features of necroptosis. Execution of cell death, but not induction of autophagy, was strictly dependent on expression of receptor-interacting protein (RIP-1) kinase and cylindromatosis (turban tumor syndrome) (CYLD), two key regulators of necroptosis. Accordingly, both inhibition of RIP-1 and interference with CYLD restored glucocorticoid resistance completely. Together with evidence for a chemosensitizing activity of obatoclax in vivo, our data provide a compelling rationale for clinical translation of this pharmacological approach into treatments for patients with refractory ALL.
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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.