Equilibrative nucleoside transporter-2 (hENT2) protein expression correlates with ex vivo sensitivity to fludarabine in chronic lymphocytic leukemia (CLL) cells
Equilibrative nucleoside transporter-2 (hENT2) protein expression correlates with ex vivo sensitivity to fludarabine in chronic lymphocytic leukemia (CLL) cells
复制标题
DOI：
10.1038/sj.leu.2403582
复制
发表时间：
2005-01-01
期刊：
影响因子：
11.4
通讯作者：
Pastor-Anglada, M
中科院分区：
文献类型：
--
作者：
Molina-Arcas, M;Marcé, S;Pastor-Anglada, M
氟达拉滨被认为是大多数慢性淋巴细胞白血病(CLL)患者的首选治疗方法。我们分析了质膜转运体在核苷类药物生物利用度中的作用以及在CLL细胞中的作用。在已知的质膜转运体中，我们先前观察到通过耳鼻咽喉管载体摄取氟达拉滨与CLL细胞对氟达拉滨的体外敏感性之间存在显著的相关性，尽管平衡的核苷转运体hENT1和hENT2的mRNA量对治疗没有任何预测性反应。在这项研究中，利用多克隆单特异性抗体，我们观察到hENT2的表达与hENT载体对氟达拉滨的摄取以及CLL细胞对氟达拉滨的体外敏感性之间存在显著的相关性。这些结果提示平衡核苷转运体hENT2在CLL患者对氟达拉滨的反应性中起作用。
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.