摘要
目的探讨药物转运蛋白人类有机阳离子转运蛋白1(OCT-1)和三磷酸腺苷结合盒蛋白B亚家族成员1(ABCB1)在慢性髓细胞性白血病(CML)中的mRNA表达水平及其对伊马替尼(IM)疗效评价的意义。方法对诊断并服用IM治疗的97例CML慢性期患者,利用实时荧光定量聚合酶链反应法(qRT-PCR)检测其骨髓细胞中OCT-1、ABCB1 mRNA的表达水平,探讨两种基因的表达量与CML患者疗效以及2年总生存率(OS)的关系。根据BCR/ABL融合基因水平将患者分为最佳反应组(n=46)、警告组(n=23)和治疗失败组(n=28);同时根据用药情况监测患者初诊时(第1天)、用药1个月(30 d)的BCR/ABL融合基因水平和ABCB1 mRNA表达量,对CML患者的疗效进行早期预测。结果最佳反应组OCT-1 mRNA表达水平高于警告组和治疗失败组(P<0.01),警告组和治疗失败组ABCB1 mRNA表达水平高于最佳反应组(P<0.01)。97例随访CML患者的2年OS为86.96%,最佳反应组(91.05%)、警告组(85.91%)和治疗失败组(80.63%)间的2年OS差异无统计学意义(P=0.49)。OCT-1 mRNA高表达组(90.41%)和低表达组(81.87%)以及ABCB1 mRNA高表达组(86.70%)和低表达组(93.13%)的2年OS差异无统计学意义(P=0.28、0.35)。通过监测患者第1天诊断和服药30 d的ABCB1 mRNA表达水平的倍数变化和BCR/ABL融合基因水平,显示ABCB1mRNA高倍数上升的患者(≥2.5,n=21)未能实现主要分子学反应(BCR/ABLIS≤0.1%,P=0.002)。同时,在第1天(P=0.423)或第30天(P=0.160),ABCB1 mRNA高表达组和低表达组的BCR/ABLIS百分比差异无统计学意义。结论 IM治疗CML患者的OCT-1、ABCB1 mRNA表达水平在疾病不同状态间存在差异,但对CML患者的2年OS没有影响。同时,早期监测ABCB1 mRNA表达水平倍数的变化为鉴定可能对IM反应不佳的患者提供了一种新的预后生物标志物。
Objective To investigate the expression levels of OCT-1 and ABCB1 mRNA and to examine the efficacy of imatinib（ IM） in chronic myeloid leukemia（ CML）. Methods Real-time quantitative polymerase chain reaction（ qRT-PCR） method was established for detecting OCT-1 and ABCB1 gene expression in 97 CML patients（ chronic phase）,and the relationship between two genes and different disease status and the overall survival rate of2 years（ OS） was investigated. Patients were divided into three groups ： optimal group（ n = 46）,warning group（ n= 23）,failure group（ n = 28） according to the BCR-ABL fusion level. The BCR-ABL fusion gene level and ABCB1 mRNA expression were measured from diagnosis to day 30 after IM therapy. The relationship between two genes and different disease status and the overall survival（ OS） of 2 years was investigated to predict the efficacy of CML patients earlier. Results The expression level of OCT-1 mRNA in the optimal group was higher than that in the warning group and the failure group（ P〈0. 01）. The expression level of ABCB1 mRNA in the warning group and the failure group was higher than that in the optimal reaction group（ P〈0. 01）. The 2-year overall survival of97 patients with CML was 86. 96%. There was no significant difference in 2-year overall survival between the optimal group（ 91. 05%）,the warning group（ 85. 91%） and the failure group（ 80. 63%）（ P = 0. 49）. At the same time,there was no significant difference between OCT-1 high expression group（ 90. 41%） and low expression group（ 81. 87%） and ABCB1 mRNA high expression group（ 86. 70%） and low expression group（ 93. 13%）（ P = 0. 28,0. 35）. By monitoring the fold changes in ABCB1 mRNA expression levels and the BCR-ABL fusion gene levels for the first day of diagnosis and day 30,it was found that patients with a high fold rise（ ≥2. 5,n = 21） were significantly less likely to achieve major molecular responses（ BCR/ABLIS≤0. 1%,P = 0. 002）. Meanwhile,th
出处
《安徽医科大学学报》
CAS
北大核心
2018年第5期764-769,共6页
Acta Universitatis Medicinalis Anhui
基金
国家自然科学基金(编号:81171605)
