Rapid in vitro testing and characterization of resistance to chemotherapeutic agents daunorubicin and cytarabine in acute myeloid leukaemia

Steven, Joshua; Taylor, Amy; Dean, Sarah; May, Jennifer; Anderson, Elizabeth

Abstract

Treatment success in leukaemia is impacted by patient resistance to chemotherapy including cytarabine (ara-C) and the anthracycline daunorubicin (DNR) requiring rapid pre-screening testing. DNR is converted to daunorubicinol (DNRol) by carbonyl reductase (CR1) in resistant patients leading to cardiomyopathy. A major mechanism for DNR resistance is p-glycoprotein (p-gp) over-expression, however the exact substrate for p-gp is unknown. The aim of this study was to characterise a novel anthracycline-resistant (K562R) cell line for mode of resistance and assess intracellular drug kinetics in a novel combined fluorescence/bioluminescence assay. IC50 values for DNR treatment were significantly higher for K562R (8.4 μM) compared to wildtype (4.8 μM) (p

• Presentation Conference Type: Conference Abstract
• Conference Name: 40th Annual Meeting of the United Kingdom Environmental Mutagen Society
• Acceptance Date: May 6, 2017
• Online Publication Date: Feb 8, 2018
• Publication Date: Nov 1, 2017
• Deposit Date: Jan 20, 2020
• Print ISSN: 0267-8357
• Publisher: Oxford University Press (OUP)
• Peer Reviewed: Peer Reviewed
• Volume: 32
• Issue: 6
• Pages: 627
• DOI: https://doi.org/10.1093/mutage/gex033
• Public URL: https://uwe-repository.worktribe.com/output/5191326