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Blood, 1 November 2004, Vol. 104, No. 9, pp. 2940-2942. Prepublished online as a Blood First Edition Paper on July 13, 2004; DOI 10.1182/blood-2004-04-1398. This Article Full Text (PDF) All Versions of this Article: 2004-04-1398v1 104/9/2940    most recent Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Burger, H. Articles by Nooter, K. Search for Related Content PubMed PubMed Citation Articles by Burger, H. Articles by Nooter, K. Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted April 13, 2004 Accepted June 13, 2004 Imatinib mesylate (STI571) is a substrate for the breast cancer resistance protein (BCRP) / ABCG2 drug pump Herman Burger*, Hans van Tol, Antonius W Boersma, Mariel Brok, Erik A Wiemer, Gerrit Stoter, and Kees Nooter Department of Medical Oncology, Erasmus Medical Center Rotterdam - Daniel den Hoed Kliniek / Josephine Nefkens Institute, Rotterdam, The Netherlands * Corresponding author; email: h.burger{at}erasmusmc.nl. Imatinib mesylate, a potent tyrosine kinase inhibitor, is successfully used in the treatment of chronic myelogenous leukemia and gastrointestinal stromal tumors. However, the intended chronic oral administration of imatinib may lead to development of cellular resistance and subsequent treatment failure. Indeed, several molecular mechanisms leading to imatinib resistance have already been reported, including overexpression of the MDR1/ABCB1 drug pump. We examined whether imatinib is a substrate for the BCRP/ABCG2 drug pump that is frequently overexpressed in human tumors. Using a panel of well-defined BCRP-overexpressing cell lines we provide the first evidence that imatinib is a substrate for BCRP, that it competes with mitoxantrone for drug export, and that BCRP-mediated efflux can be reversed by the fumitremorgin C analog Ko-143. Since BCRP is highly expressed in the gastrointestinal tract, BCRP might not only play a role in cellular resistance of tumor cells but also influence the oral bioavailability of imatinib. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: D. K. Hiwase, V. Saunders, D. Hewett, A. Frede, S. Zrim, P. Dang, L. Eadie, L. B. To, J. Melo, S. Kumar, et al. 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