دورية أكاديمية
Arginine dependency is a therapeutically exploitable vulnerability in chronic myeloid leukaemic stem cells.
| العنوان: | Arginine dependency is a therapeutically exploitable vulnerability in chronic myeloid leukaemic stem cells. |
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| المؤلفون: | Rattigan KM; Wolfson Wohl Cancer Research Centre, School of Cancer Sciences, University of Glasgow, Glasgow, UK., Zarou MM; Wolfson Wohl Cancer Research Centre, School of Cancer Sciences, University of Glasgow, Glasgow, UK., Brabcova Z; Wolfson Wohl Cancer Research Centre, School of Cancer Sciences, University of Glasgow, Glasgow, UK., Prasad B; Wolfson Wohl Cancer Research Centre, School of Cancer Sciences, University of Glasgow, Glasgow, UK., Zerbst D; Wolfson Wohl Cancer Research Centre, School of Cancer Sciences, University of Glasgow, Glasgow, UK., Sarnello D; Wolfson Wohl Cancer Research Centre, School of Cancer Sciences, University of Glasgow, Glasgow, UK., Kalkman ER; Wolfson Wohl Cancer Research Centre, School of Cancer Sciences, University of Glasgow, Glasgow, UK., Ianniciello A; Wolfson Wohl Cancer Research Centre, School of Cancer Sciences, University of Glasgow, Glasgow, UK., Scott MT; Wolfson Wohl Cancer Research Centre, School of Cancer Sciences, University of Glasgow, Glasgow, UK., Dunn K; Paul O'Gorman Leukaemia Research Centre, School of Cancer Sciences, University of Glasgow, Glasgow, UK., Shokry E; Cancer Research UK Beatson Institute, Glasgow, UK., Sumpton D; Cancer Research UK Beatson Institute, Glasgow, UK., Copland M; Paul O'Gorman Leukaemia Research Centre, School of Cancer Sciences, University of Glasgow, Glasgow, UK., Tardito S; Wolfson Wohl Cancer Research Centre, School of Cancer Sciences, University of Glasgow, Glasgow, UK.; Cancer Research UK Beatson Institute, Glasgow, UK., Vande Voorde J; Cancer Research UK Beatson Institute, Glasgow, UK., Mussai F; Institute of Immunology and Immunotherapy, University of Birmingham, Birmingham, UK., Cheng P; Bio-cancer Treatment International Ltd, Hong Kong Science Park, Shatin, New Territories, Hong Kong., Helgason GV; Wolfson Wohl Cancer Research Centre, School of Cancer Sciences, University of Glasgow, Glasgow, UK. |
| المصدر: | EMBO reports [EMBO Rep] 2023 Oct 09; Vol. 24 (10), pp. e56279. Date of Electronic Publication: 2023 Jul 25. |
| نوع المنشور: | Journal Article; Research Support, Non-U.S. Gov't |
| اللغة: | English |
| بيانات الدورية: | Publisher: Nature Publishing Group Country of Publication: England NLM ID: 100963049 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1469-3178 (Electronic) Linking ISSN: 1469221X NLM ISO Abbreviation: EMBO Rep Subsets: MEDLINE |
| أسماء مطبوعة: | Publication: 2024- : [London] : Nature Publishing Group Original Publication: Oxford, UK : Published for EMBO by Oxford University Press, 2000- |
| مواضيع طبية MeSH: | Arginine*/metabolism , Leukemia, Myelogenous, Chronic, BCR-ABL Positive*/genetics , Leukemia, Myelogenous, Chronic, BCR-ABL Positive*/drug therapy , Leukemia, Myelogenous, Chronic, BCR-ABL Positive*/metabolism, Humans ; Apoptosis ; Stem Cells/metabolism ; Neoplastic Stem Cells/metabolism |
| مستخلص: | To fuel accelerated proliferation, leukaemic cells undergo metabolic deregulation, which can result in specific nutrient dependencies. Here, we perform an amino acid drop-out screen and apply pre-clinical models of chronic phase chronic myeloid leukaemia (CML) to identify arginine as a nutrient essential for primary human CML cells. Analysis of the Microarray Innovations in Leukaemia (MILE) dataset uncovers reduced ASS1 levels in CML compared to most other leukaemia types. Stable isotope tracing reveals repressed activity of all urea cycle enzymes in patient-derived CML CD34 + cells, rendering them arginine auxotrophic. Thus, arginine deprivation completely blocks proliferation of CML CD34 + cells and induces significantly higher levels of apoptosis when compared to arginine-deprived cell lines. Similarly, primary CML cells, but not normal CD34 + samples, are particularly sensitive to treatment with the arginine-depleting enzyme, BCT-100, which induces apoptosis and reduces clonogenicity. Moreover, BCT-100 is highly efficacious in a patient-derived xenograft model, causing > 90% reduction in the number of human leukaemic stem cells (LSCs). These findings indicate arginine depletion to be a promising and novel strategy to eradicate therapy resistant LSCs. (© 2023 The Authors. Published under the terms of the CC BY 4.0 license.) |
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| معلومات مُعتمدة: | A25142 United Kingdom CRUK_ Cancer Research UK; C596/A17196 United Kingdom CRUK_ Cancer Research UK; A31287 United Kingdom CRUK_ Cancer Research UK; C57352/A29754 United Kingdom CRUK_ Cancer Research UK; A23982 United Kingdom CRUK_ Cancer Research UK |
| فهرسة مساهمة: | Keywords: amino acids; leukaemic stem cells; metabolism; therapy resistance |
| سلسلة جزيئية: | GEO GSE226887 |
| المشرفين على المادة: | 94ZLA3W45F (Arginine) |
| تواريخ الأحداث: | Date Created: 20230725 Date Completed: 20231010 Latest Revision: 20231011 |
| رمز التحديث: | 20231012 |
| مُعرف محوري في PubMed: | PMC10561355 |
| DOI: | 10.15252/embr.202256279 |
| PMID: | 37489735 |
| قاعدة البيانات: | MEDLINE |
Full Text Finder | تدمد: | 1469-3178 |
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| DOI: | 10.15252/embr.202256279 |