ArticleExperimental hematology2018
Glutaminase inhibition improves FLT3 inhibitor therapy for acute myeloid leukemia.
Article in Experimental hematology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 57 papers.
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Who cites it
57 citing papers in PubMed, 79 citations in OpenAlex.
- Glutamine Metabolism in Health and Diseases.MedComm · 2026Review
- ProteinbioRxiv : the preprint server for biology · 2026Article
- Studying clonal heterogeneity of acute myeloid leukemia under nutrient and chemotherapy stress.Blood advances · 2026Article
- High-Throughput Metabolomics in Transfusion Medicine.Methods in molecular biology (Clifton, N.J.) · 2026Article
- Small-molecule OPA1 inhibitors reverse mitochondrial adaptations to overcome therapy resistance in acute myeloid leukemia.Science advances · 2025Article
- SIRT5 inhibition impairs mitochondrial metabolism and enhances venetoclax-induced elimination of acute myeloid leukemia cells.Leukemia · 2025Article
- Metabolomic Profiling and Bioanalysis of Chronic Myeloid Leukemia: Identifying Biomarkers for Treatment Response and Disease Monitoring.Metabolites · 2025Article
- Review
- Targeting oncogenic activation of FLT3/SREBP/FASN promotes the therapeutic effect of quizartinib involving disruption of mitochondrial phospholipids.Cell death & disease · 2025Article
- Review
- Feasibility and Safety of Targeting Mitochondria Function and Metabolism in Acute Myeloid Leukemia.Current pharmacology reports · 2024Article
- Glutamine and leukemia research: progress and clinical prospects.Discover oncology · 2024Review
- Enhancing Leukemia Treatment: The Role of Combined Therapies Based on Amino Acid Starvation.Cancers · 2024Review
- Generalized metabolic flux analysis framework provides mechanism-based predictions of ophthalmic complications in type 2 diabetes patients.Health information science and systems · 2023Article
- Genomics and transcriptomic alterations of the glutamate receptors in acute myeloid leukemia.Clinical and translational science · 2023Article
- Targeting human mitochondrial NAD(P)Cellular oncology (Dordrecht, Netherlands) · 2023Article
- Exploration of Imaging Biomarkers for Metabolically-Targeted Osteosarcoma Therapy in a Murine Xenograft Model.Cancer biotherapy & radiopharmaceuticals · 2023Article
- Targeting Glutamine Metabolism as an Attractive Therapeutic Strategy for Acute Myeloid Leukemia.Current treatment options in oncology · 2023Review
- NADPH oxidase mediated oxidative stress signaling in FLT3-ITD acute myeloid leukemia.Cell death discovery · 2023Review
- Review
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
Abstract
Acute myeloid leukemia (AML) is a blood cancer that is poorly responsive to conventional cytotoxic chemotherapy and a diagnosis of AML is usually fatal. More effective and better-tolerated therapies for AML are desperately needed. Activating mutations in FMS-like tyrosine kinase 3 (FLT3) are one of the most frequently observed genetic defects in AML. FLT3 inhibitors have shown impressive anti-leukemic activity in clinical trials; however, sustained remissions using these inhibitors as monotherapy have not been achieved. Our previous studies have implicated impaired glutamine metabolism in response to FLT3 inhibitors as a dominant factor causing AML cell death. In this study, we have employed metabolic flux analysis to examine the effects of FLT3 inhibition on glutamine utilization in FLT3-mutated AML cells using stable isotope tracers. We found that the FLT3 inhibitor AC220 inhibited glutamine flux into the antioxidant factor glutathione profoundly due to defective glutamine import. We also found that the glutaminase inhibitor CB-839 similarly impaired glutathione production by effectively blocking flux of glutamine into glutamate. Moreover, the combination of AC220 with CB-839 synergized to deplete glutathione, induce mitochondrial reactive oxygen species, and cause loss of viability through apoptotic cell death. In vivo, glutaminase inhibition with CB-839 facilitated leukemic cell elimination by AC220 and improved survival significantly in a patient-derived xenograft AML mouse model. Therefore, targeting glutaminase in combination with FLT3 may represent an effective therapeutic strategy for improving treatment of FLT3-mutated AML.
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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.