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ATP结合盒转运蛋白的共表达与急性髓系白血病的不良预后相关。

Co-expression of ATP binding cassette transporters is associated with poor prognosis in acute myeloid leukemia.

作者信息

Liu Bei, Li Li-Jun, Gong Xia, Zhang Wei, Zhang Hui, Zhao Li

机构信息

The First Clinical Medical College of Lanzhou University, The First Affiliated Hospital of Lanzhou University, Lanzhou, Gansu 730000, P.R. China.

Department of Hematology, The First Affiliated Hospital of Lanzhou University, Lanzhou, Gansu 730000, P.R. China.

出版信息

Oncol Lett. 2018 May;15(5):6671-6677. doi: 10.3892/ol.2018.8095. Epub 2018 Feb 21.

Abstract

Chemotherapy failure remains a challenge when treating patients with acute myeloid leukemia (AML), who often suffer from persistent or relapsed disease. The multidrug resistance (MDR) mediated by efflux transporters of the ATP binding cassette (ABC) superfamily is a major obstacle for successful chemotherapy. The present study aimed to elucidate whether the expression of ABC transporters was associated with prognostic factors and responses to chemotherapy in patients with AML, with particular focus on whether co-expression of multiple ABC transporters resulted in a worse prognosis. In the present study, the mRNA expression levels of ABC transporters and in bone marrow (BM) mononuclear cell (MNC) samples from 96 patients with AML and in the peripheral blood (PB) MNC samples from 22 normal individuals were investigated using reverse transcription-quantitative polymerase chain reaction analysis. It was revealed that and were expressed at higher levels in patients with AML compared with normal individuals, whereas had a lower expression level. The expression of in patients with AML was significantly lower than in normal individuals (P<0.001). Patients risk status was associated with (P=0.037), (P=0.047), (P=0.015) and (P=0.027). The 4 genes were expressed a significantly higher levels in the poor response group compared with the good response group (, P=0.014; , P=0.021; , P=0.005; , P=0.009). The overexpression of the 4 ABC transporters and the complete remission rate were inversely correlated (P<0.001). These results suggest that the co-expression of multiple ABC transporters may contribute to a worse prognosis in AML.

摘要

在治疗急性髓系白血病(AML)患者时,化疗失败仍是一项挑战,这类患者常患有持续性或复发性疾病。由ATP结合盒(ABC)超家族的外排转运蛋白介导的多药耐药(MDR)是化疗成功的主要障碍。本研究旨在阐明ABC转运蛋白的表达是否与AML患者的预后因素及化疗反应相关,特别关注多种ABC转运蛋白的共表达是否会导致更差的预后。在本研究中,采用逆转录-定量聚合酶链反应分析,检测了96例AML患者骨髓(BM)单个核细胞(MNC)样本以及22名正常个体外周血(PB)MNC样本中ABC转运蛋白的mRNA表达水平。结果显示,与正常个体相比,AML患者中[具体转运蛋白1]和[具体转运蛋白2]的表达水平较高,而[具体转运蛋白3]的表达水平较低。AML患者中[具体转运蛋白4]的表达明显低于正常个体(P<0.001)。患者的风险状态与[具体转运蛋白1](P=0.037)、[具体转运蛋白2](P=0.047)、[具体转运蛋白3](P=0.015)和[具体转运蛋白4](P=0.027)相关。与良好反应组相比,这4种基因在不良反应组中的表达水平显著更高([具体转运蛋白1],P=0.014;[具体转运蛋白2],P=0.021;[具体转运蛋白3],P=0.005;[具体转运蛋白4],P=0.009)。4种ABC转运蛋白的过表达与完全缓解率呈负相关(P<0.001)。这些结果表明,多种ABC转运蛋白的共表达可能导致AML患者预后更差。

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