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Human Organic Cation Transporter 1 Protein Levels of Granulocytes Can Optimize Imatinib Therapy in Patients with Chronic Myeloid Leukemia

The human organic cation transporter 1 (hOCT1) is the major active influx protein responsible for the transport of imatinib mesylate (IM) into cells. Previous studies have used 14C-labeled IM to demonstrate a link between chronic myeloid leukemia (CML) molecular response and hOCT1 activity. However, this method is not convenient in routine clinical practice. Hence, we detected hOCT1 protein expression levels (Choct1) of peripheral blood in CML patients and evaluated the relationship between Choct1 and IM response. A total of 83 patients who were diagnosed with Philadelphia chromosome (Ph)-positive CML with IM therapy and 31 heathy donors were collected. Choct1 were detected by indirect immunofluorescent flow cytometry. The study showed that Choct1 expression was higher in healthy donors than in CML patients (n = 31, 9.11 ± 6.04; n = 35, 5.60 ± 3.74; p = 0.005). Both Choct1 and plasma IM trough concentration (Cmin, n = 83) were significantly higher in patients with major molecular response (MMR) than those without (p = 0.011; p = 0.001, respectively), and patients with Choct1 ≥4.745 and Cmin ≥1,385 ng/ml were more likely to achieve MMR. hOCT1 expression levels measured using flow cytometry is a convenient and clinically available technique. The hOCT1 expression level can be an important predictor in CML patients treated with IM. © 2014 S. Karger AG, Basel