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

J Clin Lab Anal. 2020 Sep;34(9):e23374. doi: 10.1002/jcla.23374. Epub 2020 Jul 26.

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.

Keywords: Imatinib; P-glycoprotein; chronic myeloid leukemia; multidrug resistance; resistance.

MeSH terms

  • ATP Binding Cassette Transporter, Subfamily B, Member 1 / metabolism*
  • Antineoplastic Agents / pharmacology*
  • Biomarkers, Tumor / metabolism*
  • Case-Control Studies
  • Drug Resistance, Neoplasm*
  • Female
  • Follow-Up Studies
  • Humans
  • Imatinib Mesylate / pharmacology*
  • Leukemia, Myelogenous, Chronic, BCR-ABL Positive / drug therapy*
  • Leukemia, Myelogenous, Chronic, BCR-ABL Positive / metabolism
  • Leukemia, Myelogenous, Chronic, BCR-ABL Positive / pathology
  • Male
  • Middle Aged
  • Prognosis
  • Retrospective Studies
  • Survival Rate

Substances

  • ATP Binding Cassette Transporter, Subfamily B, Member 1
  • Antineoplastic Agents
  • Biomarkers, Tumor
  • Imatinib Mesylate