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• W1929129628 abstract "L‐asparaginase (L‐ ASN ase) 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‐ ASN ase exerts cytotoxicity through targeting the Gln addiction phenotype in lymphoid cell lines. A clinically attainable intermediate dose of L‐ ASN ase induced massive apoptosis in ALL Jurkat and mantle cell lymphoma Jeko cell lines, while a low dose of L‐ ASN ase 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‐ ASN ase. L‐ ASN ase 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‐ ASN ase. The action of L‐ ASN ase 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 GLS 1 is associated with increased sensivity to L‐ ASN ase in pediatric B lineage ALL . Our results redefine L‐ ASN ase as a therapeutic agent targeting Gln addiction in certain lymphoid cells and offer an additional basis for predicting L‐ ASN ase sensitivity and engineering selective L‐ ASN ase derivatives for leukemia and lymphoma." @default.
• W1929129628 created "2016-06-24" @default.
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• W1929129628 date "2015-10-16" @default.
• W1929129628 modified "2023-10-14" @default.
• W1929129628 title "A clinically attainable dose of L‐asparaginase targets glutamine addiction in lymphoid cell lines" @default.
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• W1929129628 doi "https://doi.org/10.1111/cas.12807" @default.
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