The OPN Gene Polymorphism Confers the Susceptibility and Response to Ara-C Based Chemotherapy in Chinese AML Patients
The OPN Gene Polymorphism Confers the Susceptibility and Response to Ara-C Based Chemotherapy in Chinese AML Patients
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OPN基因多态性赋予中国急性髓系白血病患者对基于阿糖胞苷化疗的易感性和反应
DOI：
10.1159/000369685
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发表时间：
2015-01
影响因子：
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通讯作者：
Rong Zhang;Wei Yang;Ying Li;G. Zhang;Kun Yao;R. Hu;Bin Wu
中科院分区：
文献类型：
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作者：
Rong Zhang;Wei Yang;Ying Li;G. Zhang;Kun Yao;R. Hu;Bin Wu
目的：探讨骨桥蛋白（OPN）基因多态性与急性髓系白血病（AML）易感性及化疗疗效的关系。方法：收集381例初发AML患者和430例健康对照者。所有患者均接受以阿糖胞苷为基础的标准诱导化疗方案，并评价治疗反应。已经鉴定了人OPN编码基因中的几种多态性。在-156 GG>G、-443 C>T和-66 T>G 3个位点上检测了骨桥蛋白基因多态性。结果：-443C>T多态性是唯一与AML密切相关的基因型。与-443TT基因型携带者相比，我们的数据显示，-443CC基因型携带者与AML的高风险相关。-443CC基因型在不良反应组中也比良好反应组更常见。-443CC携带者更可能对AML治疗反应不良。细胞分析表明，与用-443T转染的细胞系相比，接受OPN -443C转染的白血病细胞系对Ara-C处理具有显著较低的凋亡率。结论：本研究结果提示OPN-443 C>T基因多态性可能是AML易感性和化疗反应的分子生物学指标。
Aim: To investigate the possible association between the Osteopontin (OPN) gene polymorphisms and the susceptibility and chemotherapy response of acute myeloid leukemia patients. Methods: A total of 381 patients with de nova AML and 430 healthy controls were enrolled. All patients received Ara-C-based standard induction chemotherapy regimens, and the treatment response was evaluated. Several polymorphisms in the human OPN encoding gene have been identified. The OPN) gene polymorphisms at 3 loci, namely, -156 GG>G, -443 C>T and -66T>G were determined. Results: We identified that the -443C>T polymorphism was the only one which is closely related to AML. Compared with the -443TT carriers, our data showed that the -443CC genotype carriers were significantly related to a higher risk for AML. The -443CC genotype was also more prevalent in poor response groups than in good response group. The -443CC carriers are more likely to have poor response to AML treatment. Cellular assay indicated that the leukemic cell lines receiving the OPN -443C transfection have a significantly lower apoptosis rate to Ara-C treatment compared to cell lines transfected with -443T. Conclusion: The findings of this study suggest OPN-443C>T gene polymorphism may be sued as a molecular for susceptibility and chemotherapy response of AML.