Multidrug resistance gene (mdr1) RNA levels in relation to P-glycoprotein content of leukemic cells from patients with acute leukemia.
The clinical relevance of multidrug resistance gene (mdr1) expression in tumor cells remains largely unclear. Conflicting results regarding mdr1 gene expression and clinical outcome have been obtained. Little is known about regulation of mdr1 gene expression, and the conflicting results might be explained by the fact that mdr1 RNA levels do not reflect expression at the protein level. The aim of the present study was to investigate the relationship between mdr1 RNA levels and P-glycoprotein (Pgp) content of leukemic cells from patients with acute myelogenous or lymphocytic leukemia. Mdr1 RNA levels were determined by a quantitative RNA-RNA solution hybridization method, and Pgp by Western blot technique with enhanced chemiluminescence for immunodetection. Pgp was detected in 14/14 leukemic cell samples while mdr1 RNA was detectable (> 0.15 copies/cell) in cells from only six out of the 14 patients. Mdr1 RNA levels did not correlate with the Pgp content of leukemic cells (r = 0.284, p = 0.306). Relapsed leukemias had significantly (p = 0.016) higher levels of Pgp than de novo untreated leukemias (the mean and SD optical density units were 0.56 +/- 0.18 and 0.25 +/- 0.17 respectively) while no difference was found in RNA levels. The findings support post-transcriptional level regulation of mdr1 gene expression and stress the importance of accurate determinations of the Pgp content of tumor cells in studies of the relationship between mdr1 gene expression and clinical outcome.
Department of Clinical Pharmacology, Karolinska Hospital, Stockholm, Sweden.
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Albertioni
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Gruber
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Areström
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Vitols
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000378:metabolism*; D000293:Adolescent; D000328:Adult; D000368:Aged; D000595:Amino Acid Sequence; D000918:Antibody Specificity; D000970:Antineoplastic Agents / Q000494:pharmacology; D015153:Blotting, Western; D003720:Densitometry; D018432:Drug Resistance, Multiple / Q000235:genetics*; D019008:Drug Resistance, Neoplasm; D005260:Female; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D009693:Nucleic Acid Hybridization; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism*; D012334:RNA, Neoplasm / Q000235:genetics / Q000378:metabolism*; D012680:Sensitivity and Specificity; D014407:Tumor Cells, Cultured; D014750:Vincristine / Q000494:pharmacology
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000970:Antineoplastic Agents; D012334:RNA, Neoplasm; D014750:Vincristine