ArticleThe Journal of biological chemistry2015
Rewired metabolism in drug-resistant leukemia cells: a metabolic switch hallmarked by reduced dependence on exogenous glutamine.
Article in The Journal of biological chemistry, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 47 papers.
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Who cites it
47 citing papers in PubMed, 77 citations in OpenAlex.
- Bacterioruberin fromInternational journal of molecular sciences · 2026Article
- Fueling the Fire: How Glutamine Metabolism Sustains Leukemia Growth and Resistance.BioMed (Basel, Switzerland) · 2026Article
- The role and mechanism of fatty acid oxidation in cancer drug resistance.Cell death discovery · 2025Review
- Glutamine and leukemia research: progress and clinical prospects.Discover oncology · 2024Review
- Application of omics in the diagnosis, prognosis, and treatment of acute myeloid leukemia.Biomarker research · 2024Review
- RETRACTED: High PGC-1α Expression as a Poor Prognostic Indicator in Intracranial Glioma.Biomedicines · 2024Article
- Plant-derived extracts and metabolic modulation in leukemia: a promising approach to overcome treatment resistance.Frontiers in molecular biosciences · 2023Review
- Orchestral role of lipid metabolic reprogramming in T-cell malignancy.Frontiers in oncology · 2023Review
- The Integration of Metabolomics with Other Omics: Insights into Understanding Prostate Cancer.Metabolites · 2022Review
- Prediction of prognosis and immunotherapy response of amino acid metabolism genes in acute myeloid leukemia.Frontiers in nutrition · 2022Article
- Comparison of the blood, bone marrow, and cerebrospinal fluid metabolomes in children with b-cell acute lymphoblastic leukemia.Scientific reports · 2021Article
- Effects of the Autophagy-Inhibiting Agent Chloroquine on Acute Myeloid Leukemia Cells; Characterization of Patient Heterogeneity.Journal of personalized medicine · 2021Article
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- Reprogramming of glutamine metabolism via glutamine synthetase silencing induces cisplatin resistance in A2780 ovarian cancer cells.BMC cancer · 2021Article
- The Hepatic Microenvironment Uniquely Protects Leukemia Cells through Induction of Growth and Survival Pathways Mediated by LIPG.Cancer discovery · 2021Article
- Cellular Metabolomics Profiles Associated With Drug Chemosensitivity in AML.Frontiers in oncology · 2021Article
- Metabolic Reprogramming of Chemoresistant Cancer Cells and the Potential Significance of Metabolic Regulation in the Reversal of Cancer Chemoresistance.Metabolites · 2020Review
- 2-Deoxy-D-glucose enhances the anti-cancer effects of idarubicin on idarubicin-resistant P388 leukemia cells.Oncology letters · 2020Article
- Review
Corrections and comments
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Authors and funding
9 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Cancer cells that escape induction therapy are a major cause of relapse. Understanding metabolic alterations associated with drug resistance opens up unexplored opportunities for the development of new therapeutic strategies. Here, we applied a broad spectrum of technologies including RNA sequencing, global untargeted metabolomics, and stable isotope labeling mass spectrometry to identify metabolic changes in P-glycoprotein overexpressing T-cell acute lymphoblastic leukemia (ALL) cells, which escaped a therapeutically relevant daunorubicin treatment. We show that compared with sensitive ALL cells, resistant leukemia cells possess a fundamentally rewired central metabolism characterized by reduced dependence on glutamine despite a lack of expression of glutamate-ammonia ligase (GLUL), a higher demand for glucose and an altered rate of fatty acid β-oxidation, accompanied by a decreased pantothenic acid uptake capacity. We experimentally validate our findings by selectively targeting components of this metabolic switch, using approved drugs and starvation approaches followed by cell viability analyses in both the ALL cells and in an acute myeloid leukemia (AML) sensitive/resistant cell line pair. We demonstrate how comparative metabolomics and RNA expression profiling of drug-sensitive and -resistant cells expose targetable metabolic changes and potential resistance markers. Our results show that drug resistance is associated with significant metabolic costs in cancer cells, which could be exploited using new therapeutic strategies.
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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.