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Abstract：
The introduction of tyrosine kinase inhibitors (TKI) has resulted in a significant improvement in the treatment of CML patients. However, some CML patients are resistant to imatinib therapy, the initial TKI therapy in the CML. Therefore, it is important to find prognostic markers for resistance. The OCT-1 gene involved in imatinib uptake is also suspected to cause imatinib resistance. The aim of this study was to investigate the role of OCT-1 in imatinib resistance by comparing OCT-1 expression levels in imatinib resistant and imatinib sensitive patients with chronic myeloid leukemia (CML). This study was conducted on 101 patients with CML [imatinib sensitive (n = 51) and imatinib resistant (n = 50)] who were treated with imatinib. Gene expression analysis was done using QRT-PCR. The relative expression levels of OCT-1 were calculated using 2(-ΔΔCT) method. OCT1 mRNA expression levels were 0.149 (0.011-2.532) and 0.119 (0.008-2.868) in imatinib-sensitive group and imatinib-resistant group, respectively. OCT-1 expression levels were not significantly different in the imatinib-sensitive group when compared to imatinib resistant group (p > 0.05). OCT-1 expression was also similar in BCR-ABL1 kinase domain mutation positive and negative cases (p > 0.05). The imatinib-resistant group had a higher rate of hydroxyurea or interferon-alpha treatment prior to imatinib therapy and a lower rate for first-line imatinib as the only treatment than the imatinib-sensitive group (p = 0.002 and p = 0.002, respectively). According to the results of our study, OCT-1 does not have a biomarker feature in the evaluation of imatinib response. In addition, the study should be performed in larger patient groups.
摘要：
酪氨酸激酶抑制剂(TKI)的引入使得CML患者的治疗有了显著的改善。然而,一些CML患者对伊马替尼治疗耐药，CML的初始TKI治疗。因此,寻找耐药的预后标志物很重要。参与伊马替尼摄取的OCT-1基因也被怀疑引起伊马替尼耐药。这项研究的目的是通过比较慢性粒细胞白血病（CML）伊马替尼耐药和伊马替尼敏感患者中OCT-1的表达水平，研究OCT-1在伊马替尼耐药中的作用。这项研究是对101例接受伊马替尼治疗的CML患者[伊马替尼敏感（n=51）和伊马替尼耐药（n=50）]进行的。使用QRT-PCR进行基因表达分析。使用2(-ΔΔCT)方法计算OCT-1的相对表达水平。伊马替尼敏感组和伊马替尼耐药组OCT1mRNA表达水平分别为0.149(0.011-2.532)和0.119(0.008-2.868),分别。与伊马替尼耐药组相比，伊马替尼敏感组的OCT-1表达水平没有显着差异（p>0.05）。OCT-1在BCR-ABL1激酶结构域突变阳性和阴性病例中的表达也相似(p>0.05)。与伊马替尼敏感组相比，伊马替尼耐药组在伊马替尼治疗前的羟基脲或干扰素-α治疗比率更高，而一线伊马替尼作为唯一治疗的比率更低（分别为p=0.002和p=0.002）。根据我们的研究结果,OCT-1在评估伊马替尼反应时不具有生物标志物特征。此外,本研究应在更大的患者群体中进行.
