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

Abstract

The involvement of the multidrug resistance (MDR) mediated by ABC transporter proteins P-glycoprotein (Pgp) and multidrug resistance-associated protein-1 (MRP1) overexpressions in patients with chronic myeloid leukemia (CML) are not completely understood. Pgp and MRP1 expressions and activity were analyzed in samples from 158 patients with chronic myeloid leukemia (CML). Using flow cytometry, Pgp expression was more frequently observed in early chronic (P = 0.00) and in advanced (P = 0.02) CML phases when it was compared to MRP1 expression. Variation of MDR expression and activity were observed during the CML evolution in patients previously treated with interferon and imatinib. In the K562-Lucena cell line, Pgp positive, imatinib caused an enhancing in Pgp expression at protein and mRNA levels, whereas in the Pgp negative cell line, this drug was capable of decreasing MDR1/Pgp mRNA levels. Our result emphasizes the importance of understanding the different aspects of MDR status in patients with CML when they are under investigation in determining imatinib resistance.