Overexpression of P-glycoprotein and resistance to Imatinib in chronic myeloid leukemia patients

Abstract

Background: The P-glycoprotein (P-gp) is one of the mechanisms of Imatinib (IM) resistance in chronic myeloid leukemia (CML). P-gp has been identified as an efflux pump involved in releasing of IM outside CML cells. To date, the P-gp involvement in the IM resistance development was not completely understood. Therefore, the present study aimed at measuring the P-gp expression level on lymphocytes from Tunisian patients with CML and correlating this level with a molecular response to IM. Method: The expression of P-gp on peripheral blood lymphocytes from 59 Tunisian patients with CML (27 IM responder patients vs 32 IM non-responder patients) was evaluated by flow cytometry. Result: Our finding showed significantly positive expression of P-gp in the lymphocytes from the IM non-responder group when compared to the IM-responder group (P =.001). In IM non-responder CML patients, the comparison between CCyR achievers and non-achievers showed a high mean fluorescence intensity (MFI) of P-gp expression in patients who did not achieve their CCyR (P =.001). The comparison between patients with primary and secondary resistance to IM showed an increasing MFI value in patients with primary resistance to IM (P =.001). Besides, the comparison between nilotinib-treated and dasatinib-treated patients proved a high value of MFI in nilotinib-treated patients (P =.001). Conclusion: The overexpression of P-gp on lymphocytes has significantly correlated with the failed molecular response to IM in patients with CML.