ABCB1 Overexpression Is a key initiator of resistance to tyrosine kinase inhibitors in CML cell lines

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dc.contributor.authorEadie, L.
dc.contributor.authorHughes, T.
dc.contributor.authorWhite, D.
dc.contributor.editorEaves, C.
dc.date.issued2016
dc.description.abstractThe tyrosine kinase inhibitor (TKI) imatinib has resulted in excellent responses in the majority of Chronic Myeloid Leukaemia (CML) patients; however, resistance is observed in 20-30% of patients. More recently, resistance to the second generation TKIs, nilotinib and dasatinib, has also been observed albeit at a lower incidence. ABCB1 has previously been implicated in TKI export and its overexpression linked to TKI resistance. In this study the dynamics of nilotinib resistance was studied in CML cell lines with particular focus on ABCB1 expression levels during development of resistance. Results revealed ABCB1 overexpression is likely an important initiator of nilotinib resistance in vitro. ABCB1 overexpression was also observed in cell lines as an intermediate step during development of resistance to imatinib and dasatinib in vitro. We conclude that ABCB1 overexpression may provide an initial platform to facilitate development of additional mechanisms for resistance to TKIs. This provides a rationale for investigating this phenomenon in patients undergoing TKI therapy.
dc.description.statementofresponsibilityLaura N. Eadie, Timothy P. Hughes, Deborah L. White
dc.identifier.citationPLoS ONE, 2016; 11(8):e0161470-1-e0161470-18
dc.identifier.doi10.1371/journal.pone.0161470
dc.identifier.issn1932-6203
dc.identifier.issn1932-6203
dc.identifier.orcidEadie, L. [0000-0003-1912-7602]
dc.identifier.orcidHughes, T. [0000-0002-0910-3730] [0000-0002-7990-4509]
dc.identifier.orcidWhite, D. [0000-0003-4844-333X]
dc.identifier.urihttp://hdl.handle.net/2440/106610
dc.language.isoen
dc.publisherPublic Library Science
dc.rights© 2016 Eadie et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
dc.source.urihttps://doi.org/10.1371/journal.pone.0161470
dc.subjectGene expression; protein expression; cell staining; hyperexpression techniques; kinase inhibitors; tyrosine kinase inhibitors; cell viability testing; tyrosine kinases
dc.titleABCB1 Overexpression Is a key initiator of resistance to tyrosine kinase inhibitors in CML cell lines
dc.typeJournal article
pubs.publication-statusPublished

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