Expression of breast cancer resistance protein in blast cells from patients with acute leukemia.
Breast cancer resistance protein (BCRP) is a novel member of the adenosine triphosphate-binding cassette superfamily of transport proteins. Transfection and enforced expression of BCRP in drug-sensitive cells confer resistance to mitoxantrone, doxorubicin, daunorubicin, and topotecan. We studied blast cells from 21 acute leukemia patients (20 acute myeloid leukemia, 1 acute lymphocytic leukemia) for the expression of BCRP mRNA using a quantitative reverse-transcription polymerase chain reaction assay. BCRP mRNA expression varied more than 1000-fold among the samples tested, with low or barely detectable expression in half of the samples. Seven samples (33%) had relatively high expression of BCRP mRNA. High expression of BCRP did not correlate strongly with high expression of P-glycoprotein, suggesting that BCRP may cause resistance to certain antileukemic drugs in P-glycoprotein-negative cases. High expression of BCRP mRNA is sufficiently frequent in AML to warrant more extensive investigations to determine the relation of disease subtype and treatment outcome to BCRP expression and function.
Ross
D D
DD
University of Maryland Greenebaum Cancer Center; the Department of Medicine, Division of Hematology/Oncology, University of Maryland School of Medicine, Baltimore, MD 21201, USA. dross@umgcc.umaryland.edu
Karp
J E
JE
Chen
T T
TT
Doyle
L A
LA
D000070997:ATP Binding Cassette Transporter, Subfamily G, Member 2; D018528:ATP-Binding Cassette Transporters / Q000032:analysis / Q000235:genetics*; D000208:Acute Disease; D000328:Adult; D000368:Aged; D001752:Blast Crisis / Q000378:metabolism / Q000473:pathology*; D001853:Bone Marrow / Q000378:metabolism / Q000473:pathology; D001943:Breast Neoplasms; D002478:Cells, Cultured; D005260:Female; D018922:HL-60 Cells; D006801:Humans; D007951:Leukemia, Myeloid / Q000235:genetics / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D009363:Neoplasm Proteins; D014158:Transcription, Genetic; D014407:Tumor Cells, Cultured
C116614:ABCG2 protein, human; D000070997:ATP Binding Cassette Transporter, Subfamily G, Member 2; D018528:ATP-Binding Cassette Transporters; D009363:Neoplasm Proteins