Analysis of mdr-1 gene expression in human leukemic cells by quantitative competitive PCR.
The ability to recognize the acquisition of multidrug resistance (MDR) in leukemia patients would improve our ability to predict the responsiveness of patients to chemotherapy. To quantitate the degree of MDR acquisition, we determined the amount of mdr-1 mRNA in leukemic cells from patients by competitive polymerase chain reaction (PCR) analysis. Twenty-one patients including 12 patients prior to treatment and nine relapsed patients with acute myelogenous or lymphoblastic leukemia were examined. The amount of mdr-1 gene expression in K562, K562/ADR500 cells and their mixtures showed a proportional correlation between the ratio of resistant to non-resistant cells and the amount of the mdr-1 gene. Mean mdr-1 gene expression in relapsed patients was greater than that in pretreatment patients. Patients refractory to chemotherapy (NR) showed higher levels of mdr-1 gene expression than the patients who achieved complete remission (CR). Because of the wide variations in values, no statistical differences were observed between pretreatment and relapsed patients, or CR and NR patients. These results suggest that the competitive PCR technique is a reliable method to quantitatively determine mdr-1 gene expression, but it may be difficult to predict responsiveness to chemotherapy by using this technique alone.
Kato
S
S
Department of Clinical Chemistry and Laboratory Medicine, Fukuoka University, Japan.
Ideguchi
H
H
Futata
Y
Y
Hamasaki
N
N
Umemura
T
T
Nishimura
J
J
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000096:biosynthesis* / Q000235:genetics; D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000494:pharmacology / Q000627:therapeutic use; D001483:Base Sequence; D001667:Binding, Competitive; D018432:Drug Resistance, Multiple; D005260:Female; D015973:Gene Expression Regulation, Leukemic; D006801:Humans; D007938:Leukemia / Q000188:drug therapy / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D009363:Neoplasm Proteins / Q000096:biosynthesis* / Q000235:genetics; D014411:Neoplastic Stem Cells / Q000378:metabolism*; D016133:Polymerase Chain Reaction / Q000379:methods; D014407:Tumor Cells, Cultured
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D009363:Neoplasm Proteins