Clinical resistance to chemotherapy in acute myeloid leukemia (AML) is associated with the expression of the multidrug resistance (MDR) proteins P-glycoprotein, encoded by the MDR1/ABCB1 gene, multidrug resistant-related protein (MRP/ABCC1), the lung resistance-related protein (LRP), or major vault protein (MVP), and the breast cancer resistance protein (BCRP/ABCG2). The clinical value of MDR1, MRP1, LRP/ MVP, and BCRP messenger RNA (mRNA) expression was prospectively studied in 154 newly diagnosed AML patients ≤60 years who were treated in a multicenter, randomized phase 3 trial. Expression of MDR1 and BCRP showed a negative whereas MRP1 and LRP showed a positive correlation with high white blood cell count (respectively, p<0.05, p<0.001,p<0.001 and p<0.001). Higher BCRP mRNA was associated with secondary AML (p<0.05). MDR1 and BCRP mRNA were highly significantly associated (p<0.001), as were MRP1 and LRP mRNA (p<0.001) expression. Univariate regression analyses revealed that CD34 expression, increasing MDR1 mRNA as well as MDR1/BCRP coexpression, were associated with a lower complete response (CR) rate and with worse event-free survival and overall survival. When adjusted for other prognostic actors, only CD34-related MDR1/BCRP coexpression remained significantly associated with a lower CR rate (p=0.03), thereby identifying a clinically resistant subgroup of elderly AML patients.

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Annals of Hematology
Erasmus MC: University Medical Center Rotterdam

van den Heuvel-Eibrink, M., van der Holt, B., Burnett, A., Knauf, W., Fey, M., Verhoef, G., … Sonneveld, P. (2007). CD34-related coexpression of MDR1 and BCRP indicates a clinically resistant phenotype in patients with acute myeloid leukemia (AML) of older age. Annals of Hematology, 86(5), 329–337. doi:10.1007/s00277-007-0269-7