Abstract
We have examined the expression of P-glycoprotein (P-gp) in adult T-cell leukemia (ATL) samples from 25 patients. Based on immunoblotting with a monoclonal antibody against P-gp, C219, 8 of 20 ATL patients were P-gp positive at the initial presentation. All 6 patients at the relapsed stage were P-gp positive, and refractory to chemotherapy. The expression of MDR1 mRNA in P-gp-positive ATL cells was increased at the relapsed stage of one patient. P-gp of this patient was photolabeled with [3H]azidopine and the labeling was inhibited with nimodipine, vinblastine and progesterone. These results suggest that P-gp expressed in ATL cells from patients at relapsed stage has the same binding site(s) for the drugs as that in multidrug resistant cells, and is correlated with the refractory nature of the cells to chemotherapy.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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ATP Binding Cassette Transporter, Subfamily B, Member 1
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Antibodies, Monoclonal / immunology
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Azides
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Blast Crisis / metabolism
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Cell Line
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Dihydropyridines
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Gene Expression Regulation, Leukemic
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Humans
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Immunoblotting
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Leukemia, Myelogenous, Chronic, BCR-ABL Positive / genetics
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Leukemia, Myelogenous, Chronic, BCR-ABL Positive / metabolism
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Leukemia, Myeloid, Acute / genetics
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Leukemia, Myeloid, Acute / metabolism
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Leukemia, T-Cell / genetics*
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Leukemia, T-Cell / metabolism
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Lymph Nodes / metabolism
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Lymph Nodes / pathology
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Membrane Glycoproteins / genetics*
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Membrane Glycoproteins / immunology
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Membrane Glycoproteins / metabolism
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Nimodipine / pharmacology
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Polymerase Chain Reaction
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Precursor Cell Lymphoblastic Leukemia-Lymphoma / genetics
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Precursor Cell Lymphoblastic Leukemia-Lymphoma / metabolism
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Progesterone / pharmacology
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RNA, Messenger / genetics
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RNA, Messenger / metabolism
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Tritium
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Vinblastine / pharmacology
Substances
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ATP Binding Cassette Transporter, Subfamily B, Member 1
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Antibodies, Monoclonal
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Azides
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Dihydropyridines
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Membrane Glycoproteins
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RNA, Messenger
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Tritium
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Progesterone
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Nimodipine
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Vinblastine
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azidopine