Imatinib Affects the Expression of SLC22A1 in a Non-Linear Concentration-Dependent Manner Within 24 Hours

BACKGROUND: Imatinib is actively transported into cells by the organic cation transporter (OCT1), encoded by SLC22A1. As a result, the expression of SLC22A1 is considered a prognostic marker for treatment with imatinib in patients with chronic myeloid leukemia (CML). Although limited, there is conflicting evidence indicating that imatinib may affect the expression of SLC22A1. However, thus far, no studies have investigated the effect of imatinib on SLC22A1 expression in an imatinib-sensitive cell line, which would mimic a typical clinical setting. Changes in the expression of SLC22A1 as a result of imatinib could potentially negate its usefulness as a prognostic marker. MATERIAL/METHODS: The K562 CML cell line was exposed to varying concentrations of imatinib for 24, 48, and 72 h and SLC22A1 expression was determined by quantitative real-time PCR. RESULTS: Our findings suggest that imatinib affects the expression of SLC22A1 within 24 h in a non-linear concentration-dependent manner. CONCLUSIONS: This is the first study to report on the short-term effect of imatinib on the expression of SLC22A1 in an imatinib-sensitive CML cell line. Our results suggest that imatinib affects SLC22A1 mRNA expression in a non-linear dose-dependent manner and that the changes in the expression of SLC22A1 as a result of the concentration of imatinib occur within 24 h of exposure to imatinib and remain stable thereafter for up to 72 h.