ArticleLeukemia research2015
Glutaminase activity determines cytotoxicity of L-asparaginases on most leukemia cell lines.
Article in Leukemia research, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 56 papers.
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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
56 citing papers in PubMed, 110 citations in OpenAlex.
- Randomized, Parallel Group, Open-Label Bioequivalence Trial of Intramuscular Pegaspargase in Patients With Relapsed Acute Lymphoblastic Leukemia.JCO global oncology · 2020Trial
- Article
- L-asparaginase: a review of microbial production and protein engineering with translational applications for oncology and food safety.World journal of microbiology & biotechnology · 2025Review
- Biochemical and Biophysical Divergences between TwoBiochemistry · 2025Article
- Fatty Acid Metabolism Provides an Essential Survival Signal in OxPhos and BCR DLBCL Cells.Biomedicines · 2025Article
- Metabolic Heterogeneity in Diffuse Large B-Cell Lymphoma Cells Reveals an Innovative Antimetabolic Combination Strategy.Cancers · 2025Article
- Impact of carboxymethyl dextran-asparaginase in NALM-6 cell apoptosis and autophagy.Iranian journal of veterinary research · 2025Article
- Molecular and cellular mechanisms of chemoresistance in paediatric pre-B cell acute lymphoblastic leukaemia.Cancer metastasis reviews · 2024Review
- Differential effect of asparagine and glutamine removal on three adenocarcinoma cell lines.Heliyon · 2024Article
- Production Process Optimization of RecombinantACS omega · 2024Article
- Reverse Phase Proteomic Array Profiling of Asparagine Synthetase Expression in Newly Diagnosed Acute Myeloid Leukemia.Journal of proteome research · 2024Article
- RrA, an enzyme from Rhodospirillum rubrum, is a prototype of a new family of short-chain L-asparaginases.Protein science : a publication of the Protein Society · 2024Article
- A new extracellular glutaminase and urease-free L-asparaginase from Meyerozyma guilliermondii.Brazilian journal of microbiology : [publication of the Brazilian Society for Microbiology] · 2023Article
- Article
- Mesenchymal stromal cells, metabolism, and mitochondrial transfer in bone marrow normal and malignant hematopoiesis.Frontiers in cell and developmental biology · 2023Review
- Possible mechanism of metabolic and drug resistance with L-asparaginase therapy in childhood leukaemia.Frontiers in oncology · 2023Review
- Clinical and demographic factors contributing to asparaginase-associated toxicities in children with acute lymphoblastic leukemia.Leukemia & lymphoma · 2022Article
- Tumoral microenvironment prevents de novo asparagine biosynthesis in B cell lymphoma, regardless of ASNS expression.Science advances · 2022Article
- Molecular Analysis of L-Asparaginases for Clarification of the Mechanism of Action and Optimization of Pharmacological Functions.Pharmaceutics · 2022Review
- Probing altered enzyme activity in the biochemical characterization of cancer.Bioscience reports · 2022Review
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 2 countries.
Funding
Abstract
L-Asparaginase (ASNase) is a front-line chemotherapy for acute lymphoblastic leukemia (ALL), which acts by deaminating asparagine and glutamine. To evaluate the importance of glutaminase activity, we exploited a recently developed mutant of Helicobacter pylori ASNase (dm HpA), with amino acid substitutions M121C/T169M. The mutant form has the same asparaginase activity as wild-type but lacks glutaminase activity. Wild-type and dm HpA were compared with the clinically used ASNases from Escherichia coli (l-ASP) and Erwinia chrysanthemi (ERWase). Asparaginase activity was similar for all isoforms, while glutaminase activity followed the rank order: ERWase>l-ASP>wild-type HpA>dm HpA. Cytotoxic efficacy of ASNases was tested on 11 human leukemia cell lines and two patient-derived ALL samples. Two cell lines which we had previously shown to be asparagine-dependent were equally sensitive to the asparaginase isoforms. The other nine lines and the two patient-derived samples were more sensitive to isoforms with higher glutaminase activities. ERWase was overall the most effective ASNase on all cell lines tested whereas dm HpA, having the lowest glutaminase activity, was the least effective. These data demonstrate that asparaginase activity alone may not be sufficient for ASNase cytotoxicity, and that glutaminase activity may be required for full anti-leukemic efficacy.
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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.