ArticleOncotarget2016
Inhibiting glutaminase in acute myeloid leukemia: metabolic dependency of selected AML subtypes.
Article in Oncotarget, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 117 papers.
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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.
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
117 citing papers in PubMed, 187 citations in OpenAlex.
- Glutaminase inhibition in combination with azacytidine in myelodysplastic syndromes: a phase 1b/2 clinical trial and correlative analyses.Nature cancer · 2024Trial
- Glutamine Metabolism in Health and Diseases.MedComm · 2026Review
- Plumbagin Is a PKM2 Activator That Modulates Glutamine Metabolism and Dependency in Leukemia.Metabolites · 2026Article
- Overcoming resistance to immune checkpoint inhibitor therapy in acute myeloid leukemia.Frontiers in oncology · 2026Review
- Modulating CAR-T cell exhaustion and fitness in acute myeloid leukemia: mechanistic metabolic and microenvironmental strategies.Frontiers in immunology · 2026Review
- Metabolomic Investigation of Myelodysplastic Syndromes, Multiple Myeloma, and Homozygous β-Thalassemia.Cells · 2025Review
- Small-molecule OPA1 inhibitors reverse mitochondrial adaptations to overcome therapy resistance in acute myeloid leukemia.Science advances · 2025Article
- Glutaminase activity maintains NK cell cytotoxicity through metabolic regulation of effector function.Journal of inflammation (London, England) · 2025Article
- Magnetic resonance spectroscopy-based detection of response to therapy targeting glutaminolysis in lymphoma.Blood neoplasia · 2025Article
- The role of vorasidenib in the treatment of isocitrate dehydrogenase-mutant glioma.Neuro-oncology · 2025Review
- Review
- Understanding and Targeting Metabolic Vulnerabilities in Acute Myeloid Leukemia: An Updated Comprehensive Review.Cancers · 2025Review
- Article
- Mechanism analysis and targeted therapy of IDH gene mutation in glioma.American journal of cancer research · 2025Review
- Unlocking the Heterogeneity in Acute Leukaemia: Dissection of Clonal Architecture and Metabolic Properties for Clinical Interventions.International journal of molecular sciences · 2024Review
- Chiglitazar diminishes the warburg effect through PPARγ/mTOR/PKM2 and increases the sensitivity of imatinib in chronic myeloid leukemia.Experimental hematology & oncology · 2024Article
- Metabolic dysregulation in myelodysplastic neoplasm: impact on pathogenesis and potential therapeutic targets.Medical oncology (Northwood, London, England) · 2024Review
- Feasibility and Safety of Targeting Mitochondria Function and Metabolism in Acute Myeloid Leukemia.Current pharmacology reports · 2024Article
- Dissecting L-glutamine metabolism in acute myeloid leukemia: single-cell insights and therapeutic implications.Journal of translational medicine · 2024Article
- CB-839 induces reversible dormancy in lung tumor-cells.European journal of pharmacology · 2024Article
57 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
25 authors at 8 institutions in 3 countries.
Funding
Abstract
Metabolic reprogramming has been described as a hallmark of transformed cancer cells. In this study, we examined the role of the glutamine (Gln) utilization pathway in acute myeloid leukemia (AML) cell lines and primary AML samples. Our results indicate that a subset of AML cell lines is sensitive to Gln deprivation. Glutaminase (GLS) is a mitochondrial enzyme that catalyzes the conversion of Gln to glutamate. One of the two GLS isoenzymes, GLS1 is highly expressed in cancer and encodes two different isoforms: kidney (KGA) and glutaminase C (GAC). We analyzed mRNA expression of GLS1 splicing variants, GAC and KGA, in several large AML datasets and identified increased levels of expression in AML patients with complex cytogenetics and within specific molecular subsets. Inhibition of glutaminase by allosteric GLS inhibitor bis-2-(5-phenylacetamido-1, 2, 4-thiadiazol-2-yl) ethyl sulfide or by novel, potent, orally bioavailable GLS inhibitor CB-839 reduced intracellular glutamate levels and inhibited growth of AML cells. In cell lines and patient samples harboring IDH1/IDH2 (Isocitrate dehydrogenase 1 and 2) mutations, CB-839 reduced production of oncometabolite 2-hydroxyglutarate, inducing differentiation. These findings indicate potential utility of glutaminase inhibitors in AML therapy, which can inhibit cell growth, induce apoptosis and/or differentiation in specific leukemia subtypes.
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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.