Potential mechanisms of resistance to cytarabine in AML patients.

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.
Authors	Carlos M Galmarini, Xavier Thomas, Fabien Calvo, Philippe Rousselot, Assia El Jafaari, Emeline Cros, Charles Dumontet
Journal	Leukemia research (Leuk Res) Vol. 26 Issue 7 Pg. 621-9 (Jul 2002) ISSN: 0145-2126 [Print] England
PMID	12008078 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References	Antigens, Neoplasm Antimetabolites, Antineoplastic DNA-Binding Proteins Equilibrative Nucleoside Transporter 1 Membrane Transport Proteins Neoplasm Proteins SLC29A1 protein, human Cytarabine Deoxycytidine Kinase 5'-Nucleotidase Cytidine Deaminase DNA Topoisomerases, Type I DNA Topoisomerases, Type II
Topics	5'-Nucleotidase (genetics, physiology) Acute Disease Adult Aged Antigens, Neoplasm Antimetabolites, Antineoplastic (pharmacology, therapeutic use) Cytarabine (pharmacology, therapeutic use) Cytidine Deaminase (genetics, physiology) DNA Topoisomerases, Type I (genetics, physiology) DNA Topoisomerases, Type II (genetics, physiology) DNA-Binding Proteins Deoxycytidine Kinase (genetics, physiology) Disease-Free Survival Drug Resistance, Neoplasm (genetics, physiology) Equilibrative Nucleoside Transporter 1 Female France (epidemiology) Humans Leukemia, Myeloid (drug therapy, genetics, metabolism, mortality) Life Tables Male Membrane Transport Proteins (genetics, physiology) Middle Aged Neoplasm Proteins (genetics, physiology) Neoplastic Stem Cells (drug effects, metabolism) Proportional Hazards Models Retrospective Studies Reverse Transcriptase Polymerase Chain Reaction Survival Analysis

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