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.

journal_name

Leukemia

journal_title

Leukemia

authors

Watkins DB,Hughes TP,White DL

doi

10.1038/leu.2015.170

subject

Has Abstract

pub_date

2015-10-01 00:00:00

pages

1960-9

issue

10

eissn

0887-6924

issn

1476-5551

pii

leu2015170

journal_volume

29

pub_type

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