Proposed mechanisms of imatinib resistance. 1) Denotes duplication or amplification of the Bcr-Abl sequence; 2) Denotes mutations in the Bcr-Abl sequence; 3) denotes imatinib export by the P-glycoprotein export protein; 4) denotes import of imatinib by the hOCT1 protein; 5) denotes binding of imatinib in the plasma by α1-acid glycoprotein (AGP); 6) denotes variability in the plasma level of imatinib; 7) denotes activation of alternative signaling cascades leading to Bcr-Abl independent growth; and 8) denotes alterations in the epigenetic regulation of the expression of the Bcr-Abl sequence.