Annals of Hematology, 2007, Vol.86(5), pp.329-337
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.
MDR1 ; MRP1 ; LRP ; BCRP ; Genes ; Elderly AML
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