Imatinib is a substrate for various multidrug resistance proteins

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Updated: Jun 24, 2026

A Method for Screening and Validation of Resistant Mutations Against Kinase Inhibitors
12:40

A Method for Screening and Validation of Resistant Mutations Against Kinase Inhibitors

Published on: December 7, 2014

K Czyzewski1, J Styczynski

  • 1Department of Pediatric Hematology and Oncology, Nicolaus Copernicus University, Poland. k.czyzewski@cm.umk.pl

Neoplasma
|March 25, 2009
PubMed
Abstract

Insights

Imatinib resistance in chronic myeloid leukemia (CML) is a growing concern. This study found that increased expression of P-glycoprotein (PGP), MRP1, and LRP contributes to imatinib resistance in CML K-562 cells.

Area of Science:

  • Biochemistry
  • Molecular Biology
  • Pharmacology

Background:

  • Imatinib resistance is a significant clinical challenge in chronic myeloid leukemia (CML) treatment.
  • Understanding the mechanisms of cellular drug resistance is crucial for developing effective therapies.
  • Multidrug resistance proteins (like PGP, MRP1, LRP) are implicated in cancer drug resistance.

Purpose of the Study:

  • To investigate the mechanisms of cellular drug resistance in imatinib-resistant K-562 cell lines derived from chronic myeloid leukemia (CML).
  • To assess the role of multidrug resistance proteins (PGP, MRP1, LRP) in imatinib resistance.
  • To evaluate the cytotoxicity of imatinib and other chemotherapy drugs in resistant cell lines.

Main Methods:

  • Utilized parental K-562 and imatinib-resistant K-562 cell lines.
  • Assessed drug cytotoxicity using the MTT assay, determining IC50 values.
  • Measured the expression of multidrug resistance proteins (PGP, MRP1, LRP).
  • Quantified rhodamine retention and daunorubicin accumulation to assess drug efflux activity.

Main Results:

  • Continuous imatinib exposure induced resistance, but low-dose imatinib (0.1 microM) increased sensitivity.
  • High correlation observed between PGP, MRP1, LRP expression and IC50 values for imatinib and etoposide.
  • All tested cell lines showed high resistance to cytarabine.
  • Imatinib-resistant cells exhibited lower daunorubicin accumulation, suggesting imatinib is a substrate for efflux pumps.

Conclusions:

  • Increased expression of P-glycoprotein (PGP), MRP1, and Lung Resistance Protein (LRP) is associated with imatinib resistance in CML.
  • Imatinib appears to be a substrate for these multidrug resistance proteins.
  • These findings highlight potential targets for overcoming imatinib resistance in CML patients.

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