TY - JOUR
T1 - Increased expression of the breast cancer resistance protein (BCRP) in relapsed or refractory acute myeloid leukemia (AML)
AU - Van Den Heuvel-Eibrink, M. M.
AU - Wiemer, E. A.C.
AU - Prins, A.
AU - Meijerink, J. P.P.
AU - Vossebeld, P. J.M.
AU - van der Holt, B.
AU - Pieters, R.
AU - Sonneveld, P.
N1 - Funding Information:
This study was supported by grants of the Sophia Foundation for Medical Research (SSWO grant 246), the Foundation Pediatric Oncology Center Rotterdam (Stichting SKOR), and the Kröger Society.
PY - 2002
Y1 - 2002
N2 - 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.
AB - 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.
KW - AML
KW - BCRP/MXR/ABCP
KW - LRP/MVP
KW - MDR1
KW - MRP1
KW - Relapse
UR - http://www.scopus.com/inward/record.url?scp=0036100195&partnerID=8YFLogxK
U2 - 10.1038/sj.leu.2402496
DO - 10.1038/sj.leu.2402496
M3 - Article
C2 - 11986944
AN - SCOPUS:0036100195
SN - 0887-6924
VL - 16
SP - 833
EP - 839
JO - Leukemia
JF - Leukemia
IS - 5
ER -