期刊
LEUKEMIA RESEARCH
卷 39, 期 3, 页码 355-360出版社
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.leukres.2014.12.008
关键词
CML; Imatinib resistance; Therapeutic interruptions; Membrane drug transporters; P-glycoprotein; OCT1
资金
- CIMAGO - Center of Investigation on Environment, Genetics and Oncobiology, Faculty of Medicine, University of Coimbra, Portugal
- FEDER funds through the Programa Operacional Factores de Competitividade - COMPETE
- Fundacao para a Ciencia e Tecnologia (FCT), Portugal [PEst-C/SAU/LA0001/2013-2014]
Imatinib resistance has been associated with BCR-ABL alterations, but other mechanisms might be involved, like drug transporters. Additionally, the impact of poor adherence in resistance has been little explored. Using sensitive and resistance CML cell lines, we investigated the expression of influx/efflux transporters, like P-gP and OCT1. In the therapeutic interruption model, we observed decrease of influx and increase in efflux transporters combined with BCR-ABL over-expression. Comparatively, resistant cells obtained by continuous TKI exposure only demonstrated alterations in drug's transporters. By exploring P-gP expression of resistant cells, we observed the potential of P-gP inhibitor in circumventing Imatinib resistance. Our results revealed the importance of treatment interruptions for expected response levels and show the complexity of Imatinib resistant process. Efflux transports appear as not only relevant for acquisition of resistant phenotype, but also as valid therapeutic tool for managing resistance. (C) 2014 Elsevier Ltd. All rights reserved.
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