ArticleBlood2022
Ceramide-induced integrated stress response overcomes Bcl-2 inhibitor resistance in acute myeloid leukemia.
Article in Blood, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers.
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.
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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
38 citing papers in PubMed, 45 citations in OpenAlex.
- Review
- Anti-apoptotic BCL-2 family proteins: from regulatory networks to therapeutic targeting.Oncogenesis · 2026Review
- Curcumin as a ceramide metabolism-targeting agent: Molecular mechanisms and therapeutic implications in cancer.Molecular biology reports · 2026Review
- Acid ceramidase inhibition enhances BCL-2 targeting in venetoclax-resistant acute myeloid leukemia.Blood neoplasia · 2026Article
- A Novel Potent and Selective GCN2 Inhibitor, APL-4098, Has Antileukemic Activity through Dysregulation of Mitochondrial Function.Clinical cancer research : an official journal of the American Association for Cancer Research · 2026Article
- Resistance to Targeted Therapy in AML: Current Challenges and Emerging Treatment Strategies.Journal of clinical medicine · 2026Review
- The small GTPase ARF6 regulates sphingolipid homeostasis and supports proliferation in acute myeloid leukemia.Haematologica · 2026Article
- Sphingolipid metabolism and hematologic disorders: current understanding and future directions.Frontiers in physiology · 2026Review
- ASAH1-mediated sphingolipid metabolic reprogramming in venetoclax resistance of AML: beyond the monocytic phenotypes.BMC cancer · 2025Article
- Sphingosine 1-phosphate signalling in cancer stem cells.Oncogenesis · 2025Review
- Metabolic Signature ofJournal of personalized medicine · 2025Review
- Integrated stress response activation induced by usnic acid alleviates BCL-2 inhibitor ABT-199 resistance in acute myeloid leukemia.Journal of advanced research · 2025Article
- Targeting lipid metabolism in acute myeloid leukemia: biological insights and therapeutic opportunities.Leukemia · 2025Review
- The bioactive sphingolipid playbook. A primer for the uninitiated as well as sphingolipidologists.Journal of lipid research · 2025Review
- BMAL1-depletion remodels ceramide metabolism to regulate ferroptosis and sorafenib chemosensitivity in acute myeloid leukemia.iScience · 2025Article
- Targeting ceramide transfer protein sensitizes AML to FLT3 inhibitors via a GRP78-ATF6-CHOP axis.Nature communications · 2025Article
- Current Knowledge of the Integrated Stress Response in the Development and Management of Acute Myeloid Leukemia: A Novel Target with Encouraging Progress.Drug design, development and therapy · 2025Review
- Factors affecting response and resistance to venetoclax in acute myeloid leukemia.Frontiers in oncology · 2025Review
- Advances in the application of patient-derived xenograft models in acute leukemia resistance.Cancer drug resistance (Alhambra, Calif.) · 2025Review
- Targeting YTHDF2 inhibits tumorigenesis of diffuse large B-cell lymphoma through ACER2-mediated ceramide catabolism.Journal of advanced research · 2024Article
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Authors and funding
26 authors at 5 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Inducing cell death by the sphingolipid ceramide is a potential anticancer strategy, but the underlying mechanisms remain poorly defined. In this study, triggering an accumulation of ceramide in acute myeloid leukemia (AML) cells by inhibition of sphingosine kinase induced an apoptotic integrated stress response (ISR) through protein kinase R-mediated activation of the master transcription factor ATF4. This effect led to transcription of the BH3-only protein Noxa and degradation of the prosurvival Mcl-1 protein on which AML cells are highly dependent for survival. Targeting this novel ISR pathway, in combination with the Bcl-2 inhibitor venetoclax, synergistically killed primary AML blasts, including those with venetoclax-resistant mutations, as well as immunophenotypic leukemic stem cells, and reduced leukemic engraftment in patient-derived AML xenografts. Collectively, these findings provide mechanistic insight into the anticancer effects of ceramide and preclinical evidence for new approaches to augment Bcl-2 inhibition in the therapy of AML and other cancers with high Mcl-1 dependency.
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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.