|
|
 Previous Article | Table of Contents | Next Article 
Blood, 15 May 2002, Vol. 99, No. 10, pp. 3763-3770
NEOPLASIA
Expression and activity of breast cancer resistance protein
(BCRP) in de novo and relapsed acute myeloid leukemia
Dorina M. van der Kolk,
Edo Vellenga,
George L. Scheffer,
Michael Müller,
Susan E. Bates,
Rik J. Scheper, and
Elisabeth G. E. de Vries
From the Divisions of Hematology and Medical Oncology,
University Hospital Groningen, The Netherlands; Department of
Pathology, Free University Medical Center, Amsterdam, The Netherlands;
Division of Nutrition, Metabolism, and Genomics, University Wageningen,
The Netherlands; and National Cancer Institute, Medicine Branch,
National Institutes of Health, Bethesda, MD.
Overexpression of the breast cancer resistance protein (BCRP)
efflux pump in human cancer cell lines results in resistance to a
variety of cytostatic agents. The aim of this study was to analyze BCRP
protein expression and activity in acute myeloid leukemia (AML) samples
and to determine whether it is up-regulated due to clonal selection at
relapse/refractory disease. BCRP protein expression was measured flow
cytometrically with the monoclonal antibodies BXP-34 and BXP-21 in 20 paired samples of de novo and relapsed/refractory AML.
BXP-34/immunoglobulin G1 ratios were observed of 1.6 ± 0.5 (mean
± SD, range 0.8-2.7) and BXP-21/immunoglobulin G2a ratios of
4.9 ± 3.0 (range 1.1-14.5) in the patient samples versus
9.8 ± 6.8 and 6.5 ± 2.4, respectively, in the MCF-7 cell line.
BCRP activity was determined flow cytometrically by measuring mitoxantrone accumulation in absence and presence of the inhibitor fumitremorgin C. Mitoxantrone accumulation, expressed as mean fluorescence intensity (MFI), varied between 44 and 761 MFI
(227 ± 146 MFI) and correlated inversely with BCRP expression
(r =  0.58, P < .001). Addition of
fumitremorgin C showed a small increase in mitoxantrone accumulation
(11 ± 29 MFI, n = 40) apart from the effect of PSC833 and MK-571.
No consistent up-regulation of BCRP expression or activity was observed
at relapse/refractory disease; some cases showed an increase and other
cases a decrease at relapse. Relatively high BCRP expression correlated
with immature immunophenotype, as determined by expression of the
surface marker CD34 (r = 0.54, P = .001).
In conclusion, this study shows that BCRP protein is expressed at low
but variable levels in AML, especially in immature CD34+
cells. BCRP was not consistently up-regulated in relapsed/refractory AML.
 CiteULike  Connotea  Del.icio.us  Digg  Reddit  Technorati What's this?
This article has been cited by other articles:
|
|
|
|
 
N. E. Jordanides, H. G. Jorgensen, T. L. Holyoake, and J. C. Mountford
Functional ABCG2 is overexpressed on primary CML CD34+ cells and is inhibited by imatinib mesylate
Blood,
August 15, 2006;
108(4):
1370 - 1373.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
C. S. Wilson, G. S. Davidson, S. B. Martin, E. Andries, J. Potter, R. Harvey, K. Ar, Y. Xu, K. J. Kopecky, D. P. Ankerst, et al.
Gene expression profiling of adult acute myeloid leukemia identifies novel biologic clusters for risk classification and outcome prediction
Blood,
July 15, 2006;
108(2):
685 - 696.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
Z. Benderra, A. M. Faussat, L. Sayada, J.-Y. Perrot, R. Tang, D. Chaoui, H. Morjani, C. Marzac, J.-P. Marie, and O. Legrand
MRP3, BCRP, and P-Glycoprotein Activities are Prognostic Factors in Adult Acute Myeloid Leukemia
Clin. Cancer Res.,
November 1, 2005;
11(21):
7764 - 7772.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
X.-f. Zhou, X. Yang, Q. Wang, R. A. Coburn, and M. E. Morris
EFFECTS OF DIHYDROPYRIDINES AND PYRIDINES ON MULTIDRUG RESISTANCE MEDIATED BY BREAST CANCER RESISTANCE PROTEIN: IN VITRO AND IN VIVO STUDIES
Drug Metab. Dispos.,
August 1, 2005;
33(8):
1220 - 1228.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. L. A. Sesink, I. C. W. Arts, V. C. J. de Boer, P. Breedveld, J. H. M. Schellens, P. C. H. Hollman, and F. G. M. Russel
Breast Cancer Resistance Protein (Bcrp1/Abcg2) Limits Net Intestinal Uptake of Quercetin in Rats by Facilitating Apical Efflux of Glucuronides
Mol. Pharmacol.,
June 1, 2005;
67(6):
1999 - 2006.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. H.G.P. Raaijmakers, E. P.L.M. de Grouw, L. H.H. Heuver, B. A. van der Reijden, J. H. Jansen, R. J. Scheper, G. L. Scheffer, T. J.M. de Witte, and R. A.P. Raymakers
Breast Cancer Resistance Protein in Drug Resistance of Primitive CD34+38- Cells in Acute Myeloid Leukemia
Clin. Cancer Res.,
March 15, 2005;
11(6):
2436 - 2444.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
P. Pavek, G. Merino, E. Wagenaar, E. Bolscher, M. Novotna, J. W. Jonker, and A. H. Schinkel
Human Breast Cancer Resistance Protein: Interactions with Steroid Drugs, Hormones, the Dietary Carcinogen 2-Amino-1-methyl-6-phenylimidazo(4,5-b)pyridine, and Transport of Cimetidine
J. Pharmacol. Exp. Ther.,
January 1, 2005;
312(1):
144 - 152.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
Z. Benderra, A.-M. Faussat, L. Sayada, J.-Y. Perrot, D. Chaoui, J.-P. Marie, and O. Legrand
Breast Cancer Resistance Protein and P-Glycoprotein in 149 Adult Acute Myeloid Leukemias
Clin. Cancer Res.,
December 1, 2004;
10(23):
7896 - 7902.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
D. Mahadevan and A. F. List
Targeting the multidrug resistance-1 transporter in AML: molecular regulation and therapeutic strategies
Blood,
October 1, 2004;
104(7):
1940 - 1951.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. Zhang, X. Yang, and M. E. Morris
Flavonoids Are Inhibitors of Breast Cancer Resistance Protein (ABCG2)-Mediated Transport
Mol. Pharmacol.,
May 1, 2004;
65(5):
1208 - 1216.
[Abstract]
[Full Text]
|
|
|
|
|
|
|
J van der Heijden, M C de Jong, B A C Dijkmans, W F Lems, R Oerlemans, I Kathmann, C G Schalkwijk, G L Scheffer, R J Scheper, and G Jansen
Development of sulfasalazine resistance in human T cells induces expression of the multidrug resistance transporter ABCG2 (BCRP) and augmented production of TNF{alpha}
Ann Rheum Dis,
February 1, 2004;
63(2):
138 - 143.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
T. Nakanishi, L. A. Doyle, B. Hassel, Y. Wei, K. S. Bauer, S. Wu, D. W. Pumplin, H.-B. Fang, and D. D. Ross
Functional Characterization of Human Breast Cancer Resistance Protein (BCRP, ABCG2) Expressed in the Oocytes of Xenopus laevis
Mol. Pharmacol.,
December 1, 2003;
64(6):
1452 - 1462.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. L. A. Plasschaert, D. M. van der Kolk, E. S. J. M. de Bont, W. A. Kamps, K. Morisaki, S. E. Bates, G. L. Scheffer, R. J. Scheper, E. Vellenga, and E. G. E. de Vries
The Role of Breast Cancer Resistance Protein in Acute Lymphoblastic Leukemia
Clin. Cancer Res.,
November 1, 2003;
9(14):
5171 - 5177.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
T. Brooks, H. Minderman, K. L. O'Loughlin, P. Pera, I. Ojima, M. R. Baer, and R. J. Bernacki
Taxane-based reversal agents modulate drug resistance mediated by P-glycoprotein, multidrug resistance protein, and breast cancer resistance protein
Mol. Cancer Ther.,
November 1, 2003;
2(11):
1195 - 1205.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
G. D. Leonard, T. Fojo, and S. E. Bates
The Role of ABC Transporters in Clinical Practice
Oncologist,
October 1, 2003;
8(5):
411 - 424.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. Kawabata, M. Oka, H. Soda, K. Shiozawa, K. Nakatomi, J. Tsurutani, Y. Nakamura, S. Doi, T. Kitazaki, K. Sugahara, et al.
Expression and Functional Analyses of Breast Cancer Resistance Protein in Lung Cancer
Clin. Cancer Res.,
August 1, 2003;
9(8):
3052 - 3057.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
T. Janvilisri, H. Venter, S. Shahi, G. Reuter, L. Balakrishnan, and H. W. van Veen
Sterol Transport by the Human Breast Cancer Resistance Protein (ABCG2) Expressed in Lactococcus lactis
J. Biol. Chem.,
May 30, 2003;
278(23):
20645 - 20651.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
Y. Sugimoto, S. Tsukahara, Y. Imai, Y. Sugimoto, K. Ueda, and T. Tsuruo
Reversal of Breast Cancer Resistance Protein-mediated Drug Resistance by Estrogen Antagonists and Agonists
Mol. Cancer Ther.,
January 1, 2003;
2(1):
105 - 112.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
B. L. Abbott, A.-M. Colapietro, Y. Barnes, F. Marini, M. Andreeff, and B. P. Sorrentino
Low levels of ABCG2 expression in adult AML blast samples
Blood,
December 15, 2002;
100(13):
4594 - 4601.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
