Please use this identifier to cite or link to this item: https://ahro.austin.org.au/austinjspui/handle/1/16293
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dc.contributor.authorEadie, LN-
dc.contributor.authorDang, P-
dc.contributor.authorSaunders, VA-
dc.contributor.authorYeung, David T-
dc.contributor.authorOsborn, Michael P-
dc.contributor.authorGrigg, Andrew P -
dc.contributor.authorHughes, Timothy P-
dc.contributor.authorWhite, Deborah L-
dc.date2016-07-15-
dc.date.accessioned2016-09-27T00:00:04Z-
dc.date.available2016-09-27T00:00:04Z-
dc.date.issued2016-07-15-
dc.identifier.citationLeukemia 2016; online first: 15 Julyen_US
dc.identifier.urihttps://ahro.austin.org.au/austinjspui/handle/1/16293-
dc.description.abstractTyrosine kinase inhibitor (TKI) therapy results in excellent responses in the majority of patients with chronic myeloid leukaemia. First-line imatinib treatment, with selective switching to nilotinib when patients fail to meet specific molecular targets or for imatinib intolerance, results in excellent overall molecular responses and survival. However, this strategy is less effective in cases of primary imatinib resistance; moreover, 25% of patients develop secondary resistance such that 20-35% of patients initially treated with imatinib will eventually experience treatment failure. Early identification of these patients is of high clinical relevance. Since the drug efflux transporter ABCB1 has previously been implicated in TKI resistance, we determined if early increases in ABCB1 mRNA expression (fold change from diagnosis to day 22 of imatinib therapy) predict for patient response. Indeed, patients exhibiting a high fold rise (⩾2.2, n=79) were significantly less likely to achieve early molecular response (BCR-ABL1IS ⩽10% at 3 months; P=0.001), major molecular response (P<0.0001) and MR4.5 (P<0.0001). Additionally, patients demonstrated increased levels of ABCB1 mRNA before the development of mutations and/or progression to blast crisis. Patients with high fold rise in ABCB1 mRNA were also less likely to achieve major molecular response when switched to nilotinib therapy (49% vs 82% of patients with low fold rise). We conclude that early evaluation of the fold change in ABCB1 mRNA expression may identify patients likely to be resistant to first- and second-generation TKIs and who may be candidates for alternative therapy.en_US
dc.titleThe clinical significance of ABCB1 overexpression in predicting outcome of CML patients undergoing first-line imatinib treatmenten_US
dc.typeJournal Articleen_US
dc.identifier.journaltitleLeukemiaen_US
dc.identifier.affiliationCancer Theme, South Australian Health and Medical Research Institute (SAHMRI), Adelaide, South Australia, Australiaen_US
dc.identifier.affiliationDepartment of Medicine, University of Adelaide, Adelaide, South Australia, Australiaen_US
dc.identifier.affiliationHaematology Department, SA Pathology, Adelaide, South Australia, Australiaen_US
dc.identifier.affiliationOncology Department, Women's and Children Hospital, Adelaide, South Australia, Australiaen_US
dc.identifier.affiliationClinical Haematology, Austin Health, Heidelberg, Victoria, Australiaen_US
dc.identifier.affiliationCentre for Cancer Biology, Adelaide, South Australia, Australiaen_US
dc.identifier.affiliationAustralasian Leukaemia and Lymphoma Group, Melbourne, Victoria, Australiaen_US
dc.identifier.affiliationDepartment of Paediatrics, University of Adelaide, Adelaide, South Australia, Australiaen_US
dc.identifier.pubmedurihttps://pubmed.ncbi.nlm.nih.gov/27416909en_US
dc.identifier.doi10.1038/leu.2016.179en_US
dc.type.contentTexten_US
dc.type.austinJournal Articleen_US
item.openairecristypehttp://purl.org/coar/resource_type/c_18cf-
item.cerifentitytypePublications-
item.fulltextNo Fulltext-
item.grantfulltextnone-
item.openairetypeJournal Article-
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