文章：

MATE1调控CML患者对伊马替尼的细胞摄取和敏感性

MATE1 regulates cellular uptake and sensitivity to imatinib in CML patients

原文发布日期：2016-09-16

DOI: 10.1038/bcj.2016.79

类型: Original Article

开放获取: 是

英文摘要：

Although imatinib is highly effective in the treatment of chronic myeloid leukemia (CML), 25–30% patients do not respond or relapse after initial response. Imatinib uptake into targeted cells is crucial for its molecular response and clinical effectiveness. The organic cation transporter 1 (OCT1) has been proposed to be responsible for this process, but its relevance has been discussed controversially in recent times. Here we found that the multidrug and toxin extrusion protein 1 (MATE1) transports imatinib with a manifold higher affinity. MATE1 mainly mediates the cellular uptake of imatinib into targeted cells and thereby controls the intracellular effectiveness of imatinib. Importantly, MATE1 but not OCT1 expression is reduced in total bone marrow cells of imatinib-non-responding CML patients compared with imatinib-responding patients, indicating that MATE1 but not OCT1 determines the therapeutic success of imatinib. We thus propose that imatinib non-responders could be identified early before starting therapy by measuring MATE1 expression levels.

摘要翻译： 

尽管伊马替尼在治疗慢性髓系白血病方面疗效显著，但仍有25%-30%的患者在初始治疗无效或缓解后复发。伊马替尼进入靶向细胞的摄取过程对其分子应答及临床疗效至关重要。有机阳离子转运蛋白1曾被认为介导这一过程，但近期研究对其相关性存在争议。本研究发现，多药及毒素外排蛋白1转运伊马替尼的亲和力高出数十倍。MATE1主要介导伊马替尼进入靶向细胞的摄取过程，从而调控该药物的细胞内疗效。重要的是，在伊马替尼无应答患者的全部骨髓细胞中，MATE1（而非OCT1）的表达水平较治疗应答者显著降低，这表明决定伊马替尼治疗成功的关键因素是MATE1而非OCT1。因此我们提出，通过检测MATE1表达水平可在治疗启动前早期识别伊马替尼无应答者。

原文链接：

MATE1 regulates cellular uptake and sensitivity to imatinib in CML patients