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Variation of MDR proteins expression and activity levels according to clinical status and evolution of CML patients

Flavia C Vasconcelos1, Karina L Silva, Paloma Silva de Souza

  • 1Laboratório de Hemato-Oncologia Celular e Molecular, Programa de Pesquisa em Hemato-Oncologia Molecular, Instituto Nacional de Câncer (INCA), Rio de Janeiro, Brazil.

Cytometry. Part B, Clinical Cytometry
|April 27, 2011
PubMed

Insights

Multidrug resistance (MDR) proteins P-glycoprotein (Pgp) and MRP1 are involved in chronic myeloid leukemia (CML). Pgp expression is more common in CML phases and varies with treatment, impacting imatinib resistance.

Area of Science:

  • Hematology
  • Molecular Biology
  • Pharmacology

Background:

  • Multidrug resistance (MDR) mediated by P-glycoprotein (Pgp) and multidrug resistance-associated protein-1 (MRP1) is implicated in chronic myeloid leukemia (CML).
  • The precise role and expression patterns of these transporters in CML progression and treatment response remain incompletely understood.

Purpose of the Study:

  • To investigate the expression and activity of Pgp and MRP1 in CML patients.
  • To analyze the variations in MDR expression during CML evolution and in response to therapies like interferon and imatinib.
  • To understand the impact of MDR status on imatinib resistance in CML.

Main Methods:

  • Analysis of Pgp and MRP1 expression and activity in 158 CML patient samples.
  • Flow cytometry was utilized to quantify transporter expression.
  • In vitro experiments using the K562-Lucena cell line to assess drug effects on MDR expression.

Main Results:

  • Pgp expression was significantly more frequent in early chronic and advanced CML phases compared to MRP1 expression.
  • Variations in MDR expression and activity were observed during CML evolution, particularly in patients treated with interferon and imatinib.
  • Imatinib treatment differentially affected Pgp expression in cell lines: it enhanced Pgp expression in Pgp-positive cells and decreased MDR1/Pgp mRNA in Pgp-negative cells.

Conclusions:

  • Pgp expression is prevalent in various CML phases and its activity fluctuates during disease progression and treatment.
  • Understanding MDR status is crucial for predicting and overcoming imatinib resistance in CML patients.
  • These findings highlight the complex interplay between MDR transporters, CML, and therapeutic interventions.

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