Abstract
To determine whether the human equilibrative nucleoside transporter 1 (hENT1), deoxycytidine kinase (dCK), cytoplasmic 5'-nucleotidase (5NT), cytidine deaminase (CDD), topoisomerase I (TOPO I) and topoisomerase II alpha (TOPO II) are involved in clinical resistance to cytarabine (ara-C), we analyzed the level of expression of these parameters by reverse transcriptase polymerase chain reaction (rt-PCR), at diagnosis in the blast cells of 77 acute myeloid leukemia (AML) patients treated with ara-C, including 31 for whom samples were collected at first relapse. By univariate and/or multivariate analyses, patients with expression of 5NT or hENT1 deficiency at diagnosis had significantly shorter disease-free survival (DFS) and overall survival (OS). These results suggest that expression of 5NT and reduced hENT1 in leukemic blasts at diagnosis are correlated with clinical outcome and may play a role in resistance mechanisms to ara-C in patients with AML.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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5'-Nucleotidase / genetics
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5'-Nucleotidase / physiology
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Acute Disease
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Adult
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Aged
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Antigens, Neoplasm
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Antimetabolites, Antineoplastic / pharmacology*
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Antimetabolites, Antineoplastic / therapeutic use
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Cytarabine / pharmacology*
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Cytarabine / therapeutic use
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Cytidine Deaminase / genetics
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Cytidine Deaminase / physiology
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DNA Topoisomerases, Type I / genetics
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DNA Topoisomerases, Type I / physiology
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DNA Topoisomerases, Type II / genetics
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DNA Topoisomerases, Type II / physiology
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DNA-Binding Proteins
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Deoxycytidine Kinase / genetics
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Deoxycytidine Kinase / physiology
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Disease-Free Survival
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Drug Resistance, Neoplasm / genetics
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Drug Resistance, Neoplasm / physiology*
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Equilibrative Nucleoside Transporter 1
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Female
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France / epidemiology
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Humans
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Leukemia, Myeloid / drug therapy
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Leukemia, Myeloid / genetics
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Leukemia, Myeloid / metabolism*
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Leukemia, Myeloid / mortality
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Life Tables
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Male
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Membrane Transport Proteins / genetics
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Membrane Transport Proteins / physiology
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Middle Aged
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Neoplasm Proteins / genetics
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Neoplasm Proteins / physiology*
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Neoplastic Stem Cells / drug effects
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Neoplastic Stem Cells / metabolism
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Proportional Hazards Models
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Retrospective Studies
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Reverse Transcriptase Polymerase Chain Reaction
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Survival Analysis
Substances
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Antigens, Neoplasm
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Antimetabolites, Antineoplastic
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DNA-Binding Proteins
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Equilibrative Nucleoside Transporter 1
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Membrane Transport Proteins
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Neoplasm Proteins
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SLC29A1 protein, human
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Cytarabine
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Deoxycytidine Kinase
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5'-Nucleotidase
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Cytidine Deaminase
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DNA Topoisomerases, Type I
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DNA Topoisomerases, Type II