Expression of the multidrug resistance proteins P-glycoprotein, encoded by the MDR1 gene, multidrug resistance-associated protein (MRP1) and the lung resistance-related protein or major vault protein (LRP/MVP) is associated with clinical resistance to chemotherapy in acute myeloid leukemia (AML). Recently, the breast cancer-resistant protein (BCRP), the equivalent of mitoxantrone-resistant protein (MXR) or placental ABC transporter (ABCP), was described in AML. We investigated MDR1, MRP1, LRP/MVP and BCRP mRNA expression simultaneously in 20 paired clinical AML samples from diagnosis and relapse or refractory disease, using quantitative Taqman analysis. In addition, standard assays for P-glycoprotein expression and function were performed. BCRP was the only resistance protein that was expressed at a significantly higher RNA level (median 1.7-fold, P = 0.04) at relapsed/refractory state as compared to diagnosis. In contrast, LRP/MVP mRNA expression decreased as disease evolved (P = 0.02), whereas MDR1 and MRP1 mRNA levels were not different at relapse as compared to diagnosis. Also, at the protein level no difference of MDR1 between diagnosis and relapse was found. A significant co-expression of BCRP and MDR1 was found at diagnosis (r = 0.47, P = 0.04). The present results suggest that BCRP, but not MDR1, MRP1 or I RP/MVP is associated with clinical resistant disease in AML.

Department of Pediatrics

van den Heuvel-Eibrink, M.M, Wiemer, E.A.C, Prins, A, Meijerink, J.P.P, Vossebeld, P.J, van der Holt, B, … Sonneveld, P. (2002). Increased expression of the breast cancer resistance protein (BCRP) in relapsed or refractory acute myeloid leukemia (AML). Leukemia, 16(5), 833–839. doi:10.1038/sj.leu.2402496