|
|
Prepublished online as a Blood First Edition Paper on July 25, 2002; DOI 10.1182/blood-2002-01-0271.
Previous Article | Table of Contents | Next Article 
Blood, 15 December 2002, Vol. 100, No. 13, pp. 4594-4601
NEOPLASIA
Low levels of ABCG2 expression in adult AML blast
samples
Brian L. Abbott,
Anne-Marie Colapietro,
Yuxiao Barnes,
Frank Marini,
Michael Andreeff, and
Brian P. Sorrentino
From the Department of Hematology/Oncology, St Jude
Children's Research Hospital, Memphis, TN; and the Department of Blood
and Marrow Transplantation, Section of Molecular Hematology and
Therapy, M. D. Anderson Cancer Center, Houston, TX.
Previous reports have suggested that the adenosine
triphosphate-binding cassette protein ABCG2 (breast cancer
resistance protein [BCRP], mitoxantrone resistance [MXR])
is associated with drug resistance in acute myeloid leukemia (AML). The
aims of this study were to determine the level of ABCG2 mRNA expression
necessary to produce drug resistance and to define the ABCG2 levels in
normal bone marrow (BM), peripheral blood (PB), cord blood (CB), and adult AML blast cell populations. First, using transduced clonal cell
lines expressing varying levels of ABCG2, we found that ABCG2 expression conferred resistance to mitoxantrone and topotecan, but not
to idarubicin. Next, we developed a real-time reverse transcription-polymerase chain reaction assay for measuring
ABCG2 mRNA expression levels in clinical samples. Normal BM and PB
contained low levels of ABCG2 mRNA, while higher levels were measured
in CB mononuclear cells, CD34+, and Ac133+
populations, consistent with the known stem cell enrichment in these
populations. Next, we studied the ABCG2 mRNA levels in 40 specimens
from newly diagnosed adult AML patients. Only 7% of these samples
contained ABCG2 mRNA levels within the range of our drug-resistant
clone, although another 78% were higher than normal blood and bone
marrow. Flow cytometry revealed very small subpopulations of
ABCG2-expressing cells in the cases we examined. Our data suggest that
high levels of ABCG2 mRNA expression in adult AML blast specimens are
relatively uncommon and that ABCG2 expression may be limited to a small
cell subpopulation in some cases.

CiteULike Connotea Del.icio.us Digg Reddit Technorati What's this?
This article has been cited by other articles:

|
 |

|
 |
 
M. L. Guzman, X. Li, C. A. Corbett, R. M. Rossi, T. Bushnell, J. L. Liesveld, J. Hebert, F. Young, and C. T. Jordan
Rapid and selective death of leukemia stem and progenitor cells induced by the compound 4-benzyl, 2-methyl, 1,2,4-thiadiazolidine, 3,5 dione (TDZD-8)
Blood,
December 15, 2007;
110(13):
4436 - 4444.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
J. Wang, L.-P. Guo, L.-Z. Chen, Y.-X. Zeng, and S. H. Lu
Identification of Cancer Stem Cell-Like Side Population Cells in Human Nasopharyngeal Carcinoma Cell Line
Cancer Res.,
April 15, 2007;
67(8):
3716 - 3724.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
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]
|
 |
|

|
 |

|
 |
 
M. Tadjali, S. Zhou, J. Rehg, and B. P. Sorrentino
Prospective Isolation of Murine Hematopoietic Stem Cells by Expression of an Abcg2/GFP Allele
Stem Cells,
June 1, 2006;
24(6):
1556 - 1563.
[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]
|
 |
|

|
 |

|
 |
 
S. H. Kaufmann, J. E. Karp, L. Letendre, T. J. Kottke, S. Safgren, J. Greer, I. Gojo, P. Atherton, P. A. Svingen, D. A. Loegering, et al.
Phase I and Pharmacologic Study of Infusional Topotecan and Carboplatin in Relapsed and Refractory Acute Leukemia
Clin. Cancer Res.,
September 15, 2005;
11(18):
6641 - 6649.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
M. T. Budak, O. S. Alpdogan, M. Zhou, R. M. Lavker, M.A. M. Akinci, and J. M. Wolosin
Ocular surface epithelia contain ABCG2-dependent side population cells exhibiting features associated with stem cells
J. Cell Sci.,
April 15, 2005;
118(8):
1715 - 1724.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
B. Sorrentino
The role of Abcg2 expression in hematopoietic stem cells
AACR Meeting Abstracts,
April 1, 2005;
2005(1):
1476 - 1476.
[Abstract]
|
 |
|

|
 |

|
 |
 
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]
|
 |
|

|
 |

|
 |
 
S. Zhou, Y. Zong, P. A. Ney, G. Nair, C. F. Stewart, and B. P. Sorrentino
Increased expression of the Abcg2 transporter during erythroid maturation plays a role in decreasing cellular protoporphyrin IX levels
Blood,
March 15, 2005;
105(6):
2571 - 2576.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
C. Ozvegy-Laczka, G. Varady, G. Koblos, O. Ujhelly, J. Cervenak, J. D. Schuetz, B. P. Sorrentino, G.-J. Koomen, A. Varadi, K. Nemet, et al.
Function-dependent Conformational Changes of the ABCG2 Multidrug Transporter Modify Its Interaction with a Monoclonal Antibody on the Cell Surface
J. Biol. Chem.,
February 11, 2005;
280(6):
4219 - 4227.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
C. S. de Paiva, Z. Chen, R. M. Corrales, S. C. Pflugfelder, and D.-Q. Li
ABCG2 Transporter Identifies a Population of Clonogenic Human Limbal Epithelial Cells
Stem Cells,
January 1, 2005;
23(1):
63 - 73.
[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]
|
 |
|

|
 |

|
 |
 
L. Suarez, M.-B. Vidriales, J. Garcia-Larana, G. Sanz, M.-J. Moreno, A. Lopez, S. Barrena, R. Martinez, M. Tormo, L. Palomera, et al.
CD34+ Cells from Acute Myeloid Leukemia, Myelodysplastic Syndromes, and Normal Bone Marrow Display Different Apoptosis and Drug Resistance-Associated Phenotypes
Clin. Cancer Res.,
November 15, 2004;
10(22):
7599 - 7606.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
P. Krishnamurthy, D. D. Ross, T. Nakanishi, K. Bailey-Dell, S. Zhou, K. E. Mercer, B. Sarkadi, B. P. Sorrentino, and J. D. Schuetz
The Stem Cell Marker Bcrp/ABCG2 Enhances Hypoxic Cell Survival through Interactions with Heme
J. Biol. Chem.,
June 4, 2004;
279(23):
24218 - 24225.
[Abstract]
[Full Text]
[PDF]
|
 |
|
|
|