title: OCT1 and imatinib transport in CML: is it clinically relevant?
abstract: Imatinib is a highly effective therapy for chronic phase-chronic myeloid leukaemia (CP-CML) patients; however, responses to frontline imatinib are variable. The human organic cation transporter 1 (OCT1; SLC22A1) has been reported to be the main influx transporter involved in imatinib uptake into CML cells. Furthermore, variation in the efficiency of imatinib influx via OCT1 has been demonstrated to result in the inter-patient variation observed in primary response to imatinib. Although studies have questioned the role of OCT1 in imatinib influx, these have been largely performed in non-clinical settings. Measuring both OCT1 mRNA levels and the functional activity of OCT1 in primary leukaemic cells has been demonstrated to predict molecular response and outcome in imatinib-treated CP-CML patients in several independent studies. Here, the role of OCT1 and OCT1 genetic variants in imatinib uptake and response prediction is summarised and data generated from model systems assessing the role of OCT1 in imatinib transport is discussed.
authors.affiliation: Leukaemia Research Group, Cancer Theme, South Australian Health and Medical Research Institute (SAHMRI), Adelaide, South Australia, Australia.
authors.forename: D B
authors.initials: DB
authors.lastname: Watkins
authors.affiliation: Leukaemia Research Group, Cancer Theme, South Australian Health and Medical Research Institute (SAHMRI), Adelaide, South Australia, Australia.|School of Medicine, University of Adelaide, Adelaide, South Australia, Australia.|Department of Haematology, SA Pathology, Adelaide, South Australia, Australia.
authors.forename: T P
authors.initials: TP
authors.lastname: Hughes
authors.affiliation: Leukaemia Research Group, Cancer Theme, South Australian Health and Medical Research Institute (SAHMRI), Adelaide, South Australia, Australia.|School of Medicine, University of Adelaide, Adelaide, South Australia, Australia.|Discipline of Paediatrics, University of Adelaide, Adelaide, South Australia, Australia.
authors.forename: D L
authors.initials: DL
authors.lastname: White
mesh_terms: D000818:Animals; D001692:Biological Transport; D006801:Humans; D000068877:Imatinib Mesylate / Q000493:pharmacokinetics*; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000188:drug therapy* / Q000378:metabolism* / Q000473:pathology; D027702:Organic Cation Transporter 1 / Q000378:metabolism*; D011379:Prognosis; D047428:Protein Kinase Inhibitors / Q000493:pharmacokinetics*
chemical_list: D027702:Organic Cation Transporter 1; D047428:Protein Kinase Inhibitors; D000068877:Imatinib Mesylate