Increased expression of the breast cancer resistance protein (BCRP) in relapsed or refractory acute myeloid leukemia (AML)

被引:126
作者
van den Heuvel-Eibrink, MM
Wiemer, EAC
Prins, A
Meijerink, JPP
Vossebeld, PJM
van der Holt, B
Pieters, R
Sonneveld, P
机构
[1] Sophia Childrens Univ Hosp, Dept Hematol Oncol, NL-3015 GI Rotterdam, Netherlands
[2] Erasmus Univ, Rotterdam, Netherlands
[3] Univ Rotterdam Hosp, Dept Hematol, Rotterdam, Netherlands
[4] Univ Rotterdam Hosp, Dr Daniel Den Hoed Canc Ctr, Dept Stat, Rotterdam, Netherlands
[5] Sophia Childrens Univ Hosp, Dept Pediat Hematol Oncol, NL-3015 GI Rotterdam, Netherlands
关键词
MDR1; MRP1; LRP/MVP; BCRP/MXR/ABCP; relapse; AML;
D O I
10.1038/sj.leu.2402496
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
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 Taq-man 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 LRP/MVP is associated with clinical resistant disease in AML.
引用
收藏
页码:833 / 839
页数:7
相关论文
共 68 条
[41]  
MARIE JP, 1991, BLOOD, V78, P586
[42]  
MARIE JP, 1993, LEUKEMIA, V7, P825
[43]   FLOW CYTOMETRIC DETERMINATION OF THE MULTIDRUG-RESISTANT PHENOTYPE IN ACUTE-LEUKEMIA [J].
MASLAK, P ;
HEGEWISCHBECKER, S ;
GODFREY, L ;
ANDREEFF, M .
CYTOMETRY, 1994, 17 (01) :84-93
[44]   EFFICIENT INHIBITION OF P-GLYCOPROTEIN-MEDIATED MULTIDRUG RESISTANCE WITH A MONOCLONAL-ANTIBODY [J].
MECHETNER, EB ;
RONINSON, IB .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1992, 89 (13) :5824-5828
[45]   A novel method to compensate for different amplification efficiencies between patient DNA samples in quantitative real-time PCR [J].
Meijerink, J ;
Mandigers, C ;
van de Locht, L ;
Tönnissen, E ;
Goodsaid, F ;
Raemaekers, J .
JOURNAL OF MOLECULAR DIAGNOSTICS, 2001, 3 (02) :55-61
[46]   P-glycoprotein, lung resistance-related protein and multidrug resistance associated protein in de novo acute non-lymphocytic leukaemias:: biological and clinical implications [J].
Michieli, M ;
Damiani, D ;
Ermacora, A ;
Masolini, P ;
Raspadori, D ;
Visani, G ;
Scheper, RJ ;
Baccarani, M .
BRITISH JOURNAL OF HAEMATOLOGY, 1999, 104 (02) :328-335
[47]   MDR-1 GENE AMPLIFICATION IN ACUTE LYMPHOBLASTIC-LEUKEMIA PRIOR TO ANTILEUKEMIC TREATMENT [J].
MICHIELI, M ;
GIACCA, M ;
FANIN, R ;
DAMIANI, D ;
GEROMIN, A ;
BACCARANI, M .
BRITISH JOURNAL OF HAEMATOLOGY, 1991, 78 (02) :288-289
[48]  
MITTELMAN F, 1995, INT SYSTEM HUMAN CYT
[49]  
Miyake K, 1999, CANCER RES, V59, P8
[50]   CLINICAL RELEVANCE OF IMMUNOCYTOCHEMICAL DETECTION OF MULTIDRUG-RESISTANCE-ASSOCIATED P-GLYCOPROTEIN IN HEMATOLOGIC MALIGNANCIES [J].
MUSTO, P ;
CASCAVILLA, N ;
DIRENZO, N ;
LADOGANA, S ;
LASALA, A ;
MELILLO, L ;
NOBILE, M ;
MATERA, R ;
LOMBARDI, G ;
CAROTENUTO, M .
TUMORI, 1990, 76 (04) :353-359