Targeting glutaminolysis has antileukemic activity in acute myeloid leukemia and synergizes with BCL-2 inhibition
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Key Points: Genetic- or compound CB-839–induced GAC inhibition reduces OXPHOS and has antileukemic activity in AML. GAC inhibition synergizes with BCL-2 inhibition by compound ABT-199.
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CHK1 inhibitors and glutaminase inhibitors are considered potential candidates for treating Myc-overexpressing cancers.
“Similarly, checkpoint kinase 1 (CHK1) inhibitors625–627 and glutaminase (GLS) inhibitors628–634 are also considered potential candidates for treating Myc-overexpressing cancers.”
From Recent advances in targeting the “undruggable” proteins: from drug discovery to clinical trials (2023) · cites this paper as [634]
Targeting glutaminase with chemical inhibitors decreases cancer cell proliferation in both in vitro and in vivo models.
“Mammals have two glutaminase genes, GLS and GLS2, and targeting the enzymes encoded by these genes with chemical inhibitors has been found to decrease cancer cell proliferation in both in vitro and in vivo models (Gross et al., 2014; Jacque et al., 2015; Le et al., 2012; Xiang et al., 2015; Yuneva et al., 2012).”
From Targeting Metabolism for Cancer Therapy (2017) · cites this paper as Jacque et al., 2015
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References 38 · Cited by 387
- Authors
- Jacque, N., Ronchetti, A. M., Larrue, C., Meunier, G., Birsen, R., Willems, L., Saland, E., Decroocq, J., Maciel, T. T., Lambert, M., Poulain, L., Hospital, M. A., Sujobert, P., Joseph, L., Chapuis, N., Lacombe, C., Moura, I. C., Demo, S., Sarry, J. E., Recher, C., Mayeux, P., Tamburini, J., & Bouscary, D.
- Affiliations
- Centre National de la Recherche Scientifique (FR)
- Université Toulouse III - Paul Sabatier (FR)
- Inserm (FR)
- Institut Cochin, Département Développement Reproduction Cancer, Centre National de la Recherche Scientifique, Unité Mixtes de Recherche 8104, INSERM U1016, Paris, France;
- Cancer Research Center of Toulouse, Unité Mixtes de Recherche 1037 INSERM, Toulouse, France;
- ORCID
- Venue
- Blood
- Publisher
- American Society of Hematology
- Published
- 2015-09-10
- Volume
- 126
- Issue
- 11
- Pages
- 1346-1356
- ISSN
- 0006-4971 (ISSN-L)
- 1528-0020
- PMC
- PMC4608389
- OpenAlex
- W1773238988
- Cited by
- 387
- References
- 38
- Citations by year
- 2026: 12 · 2025: 24 · 2024: 27 · 2023: 35 · 2022: 49 · 2021: 55 · 2020: 57 · 2019: 35 · 2018: 28 · 2017: 30 · 2016: 28 · 2015: 6
- FWCI
- 10.13
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Blood (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer, Hypoxia, and Metabolism
- Health Sciences › Medicine › Hematology › Acute Myeloid Leukemia Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Amino Acid Enzymes and Metabolism
- Keywords
- glutaminolysis, acute myeloid leukemia, glutaminase C, CB-839, glutamine addiction, mitochondrial oxidative phosphorylation, BCL-2 inhibition, venetoclax, synergistic drug combination, mitochondrial apoptosis, alpha-ketoglutarate, leukemia treatment
- MeSH terms
- Animals, Antineoplastic Agents, Citric Acid Cycle, Enzyme Inhibitors, Glutaminase, Glutamine, Humans, Mitochondria, Oxidative Phosphorylation, Oxygen Consumption, Sulfonamides, Thiadiazoles, Leukemia, Myeloid, Acute, Apoptosis, Bridged Bicyclo Compounds, Heterocyclic, Proto-Oncogene Proteins c-bcl-2, Xenograft Model Antitumor Assays, Benzeneacetamides, Cell Line, Tumor, Cell Proliferation, Mice, Gene Knockdown Techniques
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