Publication

Abstract : Some chronic myeloid leukemia (CML) patients do not respond to imatinib, whereas others lose an initial response. To identify potential imatinib failures, we investigated the expression of imatinib uptake transporter (human organic cation transporter 1; hOCT1) and efflux transporters (ATP-binding cassette transporters ABCB1, ABCG2, and ABCC1) using real-time quantitative reverse transcription-polymerase chain reaction in 70 CML patients. Patients with high pretreatment hOCT1 expression had superior complete cytogenetic response (CCR) rates (P=0.008), progression-free and overall survival (P=0.01 and 0.004). Pretreatment ABCB1, ABCG2, and ABCC1 levels did not correlate with treatment outcome. Regression analysis demonstrated that pretreatment hOCT1 expression was the most powerful predictor of CCR achievement at 6 months (P=0.002). Imatinib uptake into a CML cell line with high hOCT1 expression was greater than into those with modest or low expression (P=0.002). The expression of hOCT1, but not efflux transporters, is important in determining the clinical response to imatinib.