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Differential mechanisms of asparaginase resistance in B-type acute lymphoblastic leukemia and malignant natural killer cell lines
Bacterial L-asparaginase (ASNase), hydrolyzing L-asparagine (Asn), is an important drug for treating patients with acute lymphoblastic leukaemia (ALL) and natural killer (NK) cell lymphoma. Although different native or pegylated ASNase-based chemotherapy are efficient, disease relapse is frequently...
Autores principales: | , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group
2015
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5389037/ https://www.ncbi.nlm.nih.gov/pubmed/25626693 http://dx.doi.org/10.1038/srep08068 |
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author | Chien, Wei-Wen Le Beux, Céline Rachinel, Nicolas Julien, Michel Lacroix, Claire-Emmanuelle Allas, Soraya Sahakian, Pierre Cornut-Thibaut, Aurélie Lionnard, Loïc Kucharczak, Jérôme Aouacheria, Abdel Abribat, Thierry Salles, Gilles |
author_facet | Chien, Wei-Wen Le Beux, Céline Rachinel, Nicolas Julien, Michel Lacroix, Claire-Emmanuelle Allas, Soraya Sahakian, Pierre Cornut-Thibaut, Aurélie Lionnard, Loïc Kucharczak, Jérôme Aouacheria, Abdel Abribat, Thierry Salles, Gilles |
author_sort | Chien, Wei-Wen |
collection | PubMed |
description | Bacterial L-asparaginase (ASNase), hydrolyzing L-asparagine (Asn), is an important drug for treating patients with acute lymphoblastic leukaemia (ALL) and natural killer (NK) cell lymphoma. Although different native or pegylated ASNase-based chemotherapy are efficient, disease relapse is frequently observed, especially in adult patients. The neo-synthesis of Asn by asparagine synthetase (AsnS) following ASNase treatment, which involves the amino acid response and mitogen-activated protein kinase kinase/extracellular signal-regulated kinase pathways, is believed to be the basis of ASNase-resistance mechanisms. However, AsnS expression has not emerged as an accurate predictive factor for ASNase susceptibility. The aim of this study was to identify possible ASNase sensitivity/resistance-related genes or pathways using a new asparaginase, namely a pegylated r-crisantaspase, with a focus on classic Asn-compensatory responses and cell death under conditions of Asn/L-glutamine limitation. We show that, for B-ALL cell lines, changes in the expression of apoptosis-regulatory genes (especially NFκB-related genes) are associated with ASNase susceptibility. The response of malignant NK cell lines to ASNase may depend on Asn-compensatory mechanisms and other cellular processes such as cleavage of BCL2A1, a prosurvival member of the Bcl-2 protein family. These results suggest that according to cellular context, factors other than AsnS can influence ASNase susceptibility. |
format | Online Article Text |
id | pubmed-5389037 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2015 |
publisher | Nature Publishing Group |
record_format | MEDLINE/PubMed |
spelling | pubmed-53890372017-04-14 Differential mechanisms of asparaginase resistance in B-type acute lymphoblastic leukemia and malignant natural killer cell lines Chien, Wei-Wen Le Beux, Céline Rachinel, Nicolas Julien, Michel Lacroix, Claire-Emmanuelle Allas, Soraya Sahakian, Pierre Cornut-Thibaut, Aurélie Lionnard, Loïc Kucharczak, Jérôme Aouacheria, Abdel Abribat, Thierry Salles, Gilles Sci Rep Article Bacterial L-asparaginase (ASNase), hydrolyzing L-asparagine (Asn), is an important drug for treating patients with acute lymphoblastic leukaemia (ALL) and natural killer (NK) cell lymphoma. Although different native or pegylated ASNase-based chemotherapy are efficient, disease relapse is frequently observed, especially in adult patients. The neo-synthesis of Asn by asparagine synthetase (AsnS) following ASNase treatment, which involves the amino acid response and mitogen-activated protein kinase kinase/extracellular signal-regulated kinase pathways, is believed to be the basis of ASNase-resistance mechanisms. However, AsnS expression has not emerged as an accurate predictive factor for ASNase susceptibility. The aim of this study was to identify possible ASNase sensitivity/resistance-related genes or pathways using a new asparaginase, namely a pegylated r-crisantaspase, with a focus on classic Asn-compensatory responses and cell death under conditions of Asn/L-glutamine limitation. We show that, for B-ALL cell lines, changes in the expression of apoptosis-regulatory genes (especially NFκB-related genes) are associated with ASNase susceptibility. The response of malignant NK cell lines to ASNase may depend on Asn-compensatory mechanisms and other cellular processes such as cleavage of BCL2A1, a prosurvival member of the Bcl-2 protein family. These results suggest that according to cellular context, factors other than AsnS can influence ASNase susceptibility. Nature Publishing Group 2015-01-28 /pmc/articles/PMC5389037/ /pubmed/25626693 http://dx.doi.org/10.1038/srep08068 Text en Copyright © 2015, Macmillan Publishers Limited. All rights reserved http://creativecommons.org/licenses/by/4.0/ This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article's Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder in order to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ |
spellingShingle | Article Chien, Wei-Wen Le Beux, Céline Rachinel, Nicolas Julien, Michel Lacroix, Claire-Emmanuelle Allas, Soraya Sahakian, Pierre Cornut-Thibaut, Aurélie Lionnard, Loïc Kucharczak, Jérôme Aouacheria, Abdel Abribat, Thierry Salles, Gilles Differential mechanisms of asparaginase resistance in B-type acute lymphoblastic leukemia and malignant natural killer cell lines |
title | Differential mechanisms of asparaginase resistance in B-type acute lymphoblastic leukemia and malignant natural killer cell lines |
title_full | Differential mechanisms of asparaginase resistance in B-type acute lymphoblastic leukemia and malignant natural killer cell lines |
title_fullStr | Differential mechanisms of asparaginase resistance in B-type acute lymphoblastic leukemia and malignant natural killer cell lines |
title_full_unstemmed | Differential mechanisms of asparaginase resistance in B-type acute lymphoblastic leukemia and malignant natural killer cell lines |
title_short | Differential mechanisms of asparaginase resistance in B-type acute lymphoblastic leukemia and malignant natural killer cell lines |
title_sort | differential mechanisms of asparaginase resistance in b-type acute lymphoblastic leukemia and malignant natural killer cell lines |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5389037/ https://www.ncbi.nlm.nih.gov/pubmed/25626693 http://dx.doi.org/10.1038/srep08068 |
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