title: Equilibrative nucleoside transporter-2 (hENT2) protein expression correlates with ex vivo sensitivity to fludarabine in chronic lymphocytic leukemia (CLL) cells.
abstract: Fludarabine is considered the treatment of choice for most patients with chronic lymphocytic leukemia (CLL). We have analyzed the role of plasma membrane transporters in nucleoside-derived drug bioavailability and action in CLL cells. Among the known plasma membrane transporters, we have previously observed a significant correlation between fludarabine uptake via ENT carriers and ex vivo sensitivity of CLL cells to fludarabine, although mRNA amounts of the equilibrative nucleoside transporters hENT1 and hENT2 do not show any predictive response to treatment. In this study, using polyclonal monospecific antibodies we have observed a significant correlation between the expression of hENT2 by Western blot and fludarabine uptake via hENT carriers and also with ex vivo sensitivity of CLL cells to fludarabine. These results suggest that the equilibrative nucleoside transporter hENT2 plays a role in fludarabine responsiveness in CLL patients.
authors.affiliation: Departament de Bioquímica i Biologia Molecular, Universitat de Barcelona, E-08028 Barcelona, Spain.
authors.forename: M
authors.initials: M
authors.lastname: Molina-Arcas
authors.forename: S
authors.initials: S
authors.lastname: Marcé
authors.forename: N
authors.initials: N
authors.lastname: Villamor
authors.forename: I
authors.initials: I
authors.lastname: Huber-Ruano
authors.forename: F J
authors.initials: FJ
authors.lastname: Casado
authors.forename: B
authors.initials: B
authors.lastname: Bellosillo
authors.forename: E
authors.initials: E
authors.lastname: Montserrat
authors.forename: J
authors.initials: J
authors.lastname: Gil
authors.forename: D
authors.initials: D
authors.lastname: Colomer
authors.forename: M
authors.initials: M
authors.lastname: Pastor-Anglada
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D015153:Blotting, Western; D033722:Equilibrative-Nucleoside Transporter 2 / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000473:pathology*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014407:Tumor Cells, Cultured; D014740:Vidarabine / Q000031:analogs & derivatives* / Q000494:pharmacology*
chemical_list: D000970:Antineoplastic Agents; D033722:Equilibrative-Nucleoside Transporter 2; D012333:RNA, Messenger; C438654:SLC29A2 protein, human; D014740:Vidarabine; C024352:fludarabine