ArticleCancer science2015
A clinically attainable dose of L-asparaginase targets glutamine addiction in lymphoid cell lines.
Article in Cancer science, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 42 citations in OpenAlex.
- Repurposing Asparaginase Therapy to Target Cisplatin-Resistant Cancer Cells.Fundamental & clinical pharmacology · 2025Article
- Asparagine availability controls germinal center B cell homeostasis.Science immunology · 2024Article
- Metabolic regulation of the immune system in health and diseases: mechanisms and interventions.Signal transduction and targeted therapy · 2024Review
- Extranodal natural killer/T-cell lymphoma with hepatosplenic involvement: a retrospective study of a consecutive 14-year case series.Annals of hematology · 2023Article
- Targeting glutaminase to starve lymphoma cells.Haematologica · 2023Article
- Therapeutic impact of purified Trichoderma viride L-asparaginase in murine model of liver cancer and in vitro Hep-G2 cell line.Journal, genetic engineering & biotechnology · 2023Article
- Metabolic Reprogramming and Potential Therapeutic Targets in Lymphoma.International journal of molecular sciences · 2023Review
- Targeting Glutaminolysis Shows Efficacy in Both Prednisolone-Sensitive and in Metabolically Rewired Prednisolone-Resistant B-Cell Childhood Acute Lymphoblastic Leukaemia Cells.International journal of molecular sciences · 2023Article
- Metronomic Chemotherapy in Pediatric Oncology: From Preclinical Evidence to Clinical Studies.Journal of clinical medicine · 2022Review
- Structural and biophysical studies of new L-asparaginase variants: lessons from random mutagenesis of the prototypic Escherichia coli Ntn-amidohydrolase.Acta crystallographica. Section D, Structural biology · 2022Article
- Biochemical and Biological Evaluation of an L-Asparaginase from Isolated Escherichia coli MF-107 as an Anti-Tumor Enzyme on MCF7 Cell LineIranian biomedical journal · 2022Article
- Article
- Asparagine, colorectal cancer, and the role of sex, genes, microbes, and diet: A narrative review.Frontiers in molecular biosciences · 2022Review
- Activation of proline biosynthesis is critical to maintain glutamate homeostasis during acute methamphetamine exposure.Scientific reports · 2021Article
- Amino acid depletion triggered by ʟ-asparaginase sensitizes MM cells to carfilzomib by inducing mitochondria ROS-mediated cell death.Blood advances · 2020Article
- Immunometabolism: new insights and lessons from antigen-directed cellular immune responses.Seminars in immunopathology · 2020Review
- Concurrent use of rabacfosadine and L-asparaginase for relapsed or refractory multicentric lymphoma in dogs.Journal of veterinary internal medicine · 2020Article
- Pharmacogenetics of asparaginase in acute lymphoblastic leukemia.Cancer drug resistance (Alhambra, Calif.) · 2019Review
- Increased Absolute Glutamate Concentrations and Glutamate-to-Creatine Ratios in Patients With Methamphetamine Use Disorders.Frontiers in psychiatry · 2018Article
- A clinically attainable dose of L-asparaginase targets glutamine addiction in lymphoid cell lines.Cancer science · 2015Article
Corrections and comments
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Authors and funding
10 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
L-asparaginase (L-ASNase) is an important branch of chemotherapy for acute lymphoblastic leukemia (ALL) and some types of non-Hodgkin's lymphoma, including natural killer (NK)-cell lymphoma. Although it mediates hydrolysis of asparagine (Asn) and glutamine (Gln), which are variably required for cancer cell survival, the relative contribution of Asn and Gln depletion to the anti-tumor activity in therapeutic doses is unclear in ALL and malignant lymphoma. Here we demonstrate that L-ASNase exerts cytotoxicity through targeting the Gln addiction phenotype in lymphoid cell lines. A clinically attainable intermediate dose of L-ASNase induced massive apoptosis in ALL Jurkat and mantle cell lymphoma Jeko cell lines, while a low dose of L-ASNase effectively killed NK-cell lymphoma cells. In the lymphoid cell lines Jurkat and Jeco, deprivation of Gln but not Asn specifically suppressed cell growth and survival, and phenocopied the action of L-ASNase. L-ASNase treatment and Gln deprivation dramatically disrupted the refilling of the tricarboxylic acid (TCA) cycle by intracellular glutamate (Glu) and disturbed the mitochondrial integrity, which were alleviated by various anaplerotic TCA cycle intermediates, suggesting a direct contribution of glutaminase activity of L-ASNase. The action of L-ASNase differs between Jurkat cells and NK-cell lymphoma cells, according to their dependence on Gln and Asn. Furthermore, we observed that high expression of glutaminase GLS1 is associated with increased sensivity to L-ASNase in pediatric B lineage ALL. Our results redefine L-ASNase as a therapeutic agent targeting Gln addiction in certain lymphoid cells and offer an additional basis for predicting L-ASNase sensitivity and engineering selective L-ASNase derivatives for leukemia and lymphoma.
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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.