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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

Authors

Joshua Steven

Amy Taylor

Sarah Dean Sarah4.Dean@uwe.ac.uk
Senior Lecturer in Biomedical Science

Jennifer May Jennifer2.May@uwe.ac.uk
Senior Lecturer in Biomedical Science



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

Citation

May, J., Steven, J., Taylor, A., Dean, S., & Anderson, E. (2017). Rapid in vitro testing and characterization of resistance to chemotherapeutic agents daunorubicin and cytarabine in acute myeloid leukaemia. Mutagenesis, 32(6), 627. https://doi.org/10.1093/mutage/gex033

Journal Article Type Meeting 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