Quantitative assessment of the sensitivity of dormant AML cells to the BAD mimetics ABT-199 and ABT-737

Yu, Ning and Seedhouse, Claire and Russell, Nigel and Pallis, Monica (2018) Quantitative assessment of the sensitivity of dormant AML cells to the BAD mimetics ABT-199 and ABT-737. Leukemia and Lymphoma, 12 . pp. 1-7. ISSN 1029-2403

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Abstract

Cells from patients with acute myeloid leukaemia (AML) that remain dormant and protected by stromal cells may escape effects of chemotherapy. We modelled dormancy in vitro and investigated the ability of Bcl-2 inhibitors ABT-199 and ABT-737 to overcome chemoprotection of dormant cells. CD34-enriched primary AML cells with aberrant leukaemia-associated phenotypes (LAPs) were cultured on stromal cells. The chemosensitivity of dormant (PKH26high), CD34+, LAP+ cells was ascertained by 5-colour flow cytometric counting after 12 days. The PKH26high, CD34+, LAP+ subset retained clonogenic capacity. The dormant fraction was completely resistant to ara-C (P=0.007). However, ABT-199 and ABT-737 were able to reduce the dormant fraction by 84% and 80% respectively of their effects on proliferating counterparts. In conclusion, we have elaborated a system for quantifying chemosensitivity in LAP+ dormant leukaemia cells thought to contribute to disease relapse, and shown sensitivity of dormant LAP+ cells to ABT-199 and ABT-737 in this system.

Item Type: Article
Additional Information: This is an Accepted Manuscript of an article published by Taylor & Francis in Leukemia and Lymphoma on 12 Feb 2018, available online: http://www.tandfonline.com/10.1080/10428194.2018.1434884.
Keywords: AML; ABT-199; ABT-737; dormancy
Schools/Departments: University of Nottingham, UK > Faculty of Medicine and Health Sciences > School of Medicine > Division of Cancer and Stem Cells
Identification Number: https://doi.org/10.1080/10428194.2018.1434884
Depositing User: Seedhouse, Claire
Date Deposited: 28 Mar 2018 11:19
Last Modified: 28 Mar 2018 12:25
URI: http://eprints.nottingham.ac.uk/id/eprint/50748

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