Abstract
AraC resistance in vitro is explained by inactivation of dCK, while resistance to DNR is described by overexpression of multidrug efflux pumps like Pgp or MRP. Thus far, no correlation between resistance mechanisms in vitro and in patients with AML has been documented. We generated AraC and DNR double resistant cell lines to investigate resistance mechanisms of both agents. In these cell lines involvement of dCK was extensively investigated and Pgp expression and activity was determined. Our data implicate that similar resistance mechanisms like inactivation of dCK coincided by alternatively spliced dCK forms and overexpression of Pgp are induced in single-as well as in double resistant leukemic cell lines.
Publication types
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Comparative Study
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Research Support, Non-U.S. Gov't
MeSH terms
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2-Chloroadenosine / analogs & derivatives*
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2-Chloroadenosine / pharmacology
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ATP Binding Cassette Transporter, Subfamily B, Member 1 / biosynthesis*
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ATP Binding Cassette Transporter, Subfamily B, Member 1 / genetics
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Alternative Splicing
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Animals
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Azacitidine / analogs & derivatives*
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Azacitidine / pharmacology
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Biological Transport / drug effects
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Biological Transport / genetics
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Buthionine Sulfoximine / pharmacology
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Calcium Channel Blockers / pharmacology
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Cytarabine / pharmacology*
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DNA Mutational Analysis
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DNA, Neoplasm / genetics
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Daunorubicin / pharmacology*
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Decitabine
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Deoxyadenosines / pharmacology
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Deoxycytidine Kinase / antagonists & inhibitors*
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Deoxycytidine Kinase / biosynthesis
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Deoxycytidine Kinase / genetics
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Drug Resistance, Multiple / genetics*
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Drug Resistance, Neoplasm / genetics*
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Glutathione / antagonists & inhibitors
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Humans
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Idarubicin / pharmacology
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Leukemia / genetics
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Leukemia / pathology*
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Methotrexate / pharmacology
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Neoplasm Proteins / antagonists & inhibitors*
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Neoplasm Proteins / biosynthesis
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Neoplasm Proteins / genetics
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Rats
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Reverse Transcriptase Polymerase Chain Reaction
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Tumor Cells, Cultured / drug effects
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Verapamil / pharmacology
Substances
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ATP Binding Cassette Transporter, Subfamily B, Member 1
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Calcium Channel Blockers
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DNA, Neoplasm
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Deoxyadenosines
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Neoplasm Proteins
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Cytarabine
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2-Chloroadenosine
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Buthionine Sulfoximine
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Decitabine
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Verapamil
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Deoxycytidine Kinase
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Glutathione
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2-chloro-3'-deoxyadenosine
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Azacitidine
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Methotrexate
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Idarubicin
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Daunorubicin