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Prepublished online as a Blood First Edition Paper on October 31, 2002; DOI 10.1182/blood-2002-07-2236. This Article Full Text Full Text (PDF) All Versions of this Article: 2002-07-2236v1 101/6/2328    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Molina-Arcas, M. Articles by Pastor-Anglada, M. Search for Related Content PubMed PubMed Citation Articles by Molina-Arcas, M. Articles by Pastor-Anglada, M. Related Collections Neoplasia Gene Expression Clinical Trials and Observations Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  Blood, 15 March 2003, Vol. 101, No. 6, pp. 2328-2334 NEOPLASIA Fludarabine uptake mechanisms in B-cell chronic lymphocytic leukemia Míriam Molina-Arcas, Beatriz Bellosillo, F. Javier Casado, Emili Montserrat, Joan Gil, Dolors Colomer, and Marçal Pastor-Anglada From the Departament de Bioquímica i Biologia Molecular, Universitat de Barcelona, Barcelona, Spain; Unitat d'Hematopatologia and Servei d'Hematologia, Hospital Clínic, Institut d'Investigacions Biomèdiques Agusti Pi i Sunyer (IDIBAPS), Barcelona, Spain; and Departament de Ciències Fisiològiques II, Campus de Bellvitge, Universitat de Barcelona, Hospitalet, Spain. Nucleoside derivatives are currently used in the treatment of hematologic malignancies. Although intracellular events involved in the pharmacologic action of these compounds have been extensively studied, the role of plasma membrane transporters in nucleoside-derived drug bioavailability and action in leukemia cells has not been comprehensively addressed. We have monitored the amounts of mRNA for the 5 nucleoside transporter isoforms cloned so far (CNT1, CNT2, CNT3, ENT1, and ENT2) in several human cell types and in normal human leukocytes. We then examined the expression patterns of these plasma membrane proteins in patients with chronic lymphocytic leukemia (CLL) and correlated them with in vitro fludarabine cytotoxicity. Despite a huge individual variability in the mRNA amounts for every transporter gene expressed in CLL cells (CNT2, CNT3, ENT1, and ENT2), no relationship between mRNA levels and in vitro fludarabine cytotoxicity was observed. Fludarabine accumulation in CLL cells was mostly, if not exclusively, mediated by ENT-type transporters whose biologic activity was clearly correlated with fludarabine cytotoxicity, which reveals a role of ENT-mediated uptake in drug responsiveness in patients with CLL. © 2003 by The American Society of Hematology.   CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: K. D. Ibarra and J. K. Pfeiffer Reduced Ribavirin Antiviral Efficacy via Nucleoside Transporter-Mediated Drug Resistance J. Virol., May 1, 2009; 83(9): 4538 - 4547. [Abstract] [Full Text] [PDF] M. Lopez-Guerra, G. Roue, P. Perez-Galan, R. Alonso, N. Villamor, E. Montserrat, E. Campo, and D. Colomer p65 Activity and ZAP-70 Status Predict the Sensitivity of Chronic Lymphocytic Leukemia Cells to the Selective I{kappa}B Kinase Inhibitor BMS-345541 Clin. Cancer Res., April 15, 2009; 15(8): 2767 - 2776. [Abstract] [Full Text] [PDF] S. W. Yee, J. E. 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[Abstract] [Full Text] [PDF] G. Minuesa, S. Purcet, I. Erkizia, M. Molina-Arcas, M. Bofill, N. Izquierdo-Useros, F. J. Casado, B. Clotet, M. Pastor-Anglada, and J. Martinez-Picado Expression and Functionality of Anti-Human Immunodeficiency Virus and Anticancer Drug Uptake Transporters in Immune Cells J. Pharmacol. Exp. Ther., February 1, 2008; 324(2): 558 - 567. [Abstract] [Full Text] [PDF] E. Errasti-Murugarren, P. Cano-Soldado, M. Pastor-Anglada, and F. J. Casado Functional Characterization of a Nucleoside-Derived Drug Transporter Variant (hCNT3C602R) Showing Altered Sodium-Binding Capacity Mol. Pharmacol., February 1, 2008; 73(2): 379 - 386. [Abstract] [Full Text] [PDF] R. P. Owen, L. L. Lagpacan, T. R. Taylor, M. De La Cruz, C. C. Huang, M. Kawamoto, S. J. Johns, D. Stryke, T. E. Ferrin, and K. M. Giacomini FUNCTIONAL CHARACTERIZATION AND HAPLOTYPE ANALYSIS OF POLYMORPHISMS IN THE HUMAN EQUILIBRATIVE NUCLEOSIDE TRANSPORTER, ENT2 Drug Metab. 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