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生存素及其剪接变体在儿童急性淋巴细胞白血病中的表达

Expression of Survivin and Its Splice Variants in Pediatric Acute Lymphoblastic Leukemia.

作者信息

Eren-Keleş Efsun, Karabulut Halil Gürhan, Çakmaklı Hasan Fatih, Adaklı Başak, Köse Serdar Kenan, Uğur-Dinçaslan Handan, Yavuz Gülsan, Ertem Mehmet, Tükün Ajlan

机构信息

Central Laboratory, Biotechnology Institute, Ankara University, Ankara, Turkey.

Department of Medical Genetics, School of Medicine, Ankara University, Ankara, Turkey.

出版信息

Genet Test Mol Biomarkers. 2018 Dec;22(12):680-685. doi: 10.1089/gtmb.2018.0152. Epub 2018 Nov 29.

Abstract

Survivin is involved in the inhibition of apoptosis and the regulation of cell division. In addition to wild-type survivin (survivin-wt), at least four splice variants with differential functions (ΔEx3 and 3B antiapoptotic, and 2α and 2B proapoptotic) have been identified. Survivin is highly expressed in several cancers, including hematological malignancies. Although acute lymphoblastic leukemia (ALL) is the most frequent malignancy in children, studies that investigated survivin expression in ALL are limited, and there is no study on 3B and 2α expression in ALL. Therefore the expression of survivin-wt and its splice variants was investigated in pediatric B-cell ALL patients. The expression of survivin-wt and its four splice variants was investigated by quantitative real-time polymerase chain reaction in archival RNA samples of 35 pediatric B-cell ALL patients. Patients were divided into high- and standard-risk groups according to age, white blood cell count, extramedullary involvement, and genetic risk factors; expression of survivin variants was compared between these two risk groups. We found that the ratio of survivin-ΔEx3/wild type (WT) expression was higher in the low-risk group than in the high-risk group. Comparative analysis between the high- and low-risk B-cell ALL groups indicated that the survivin-ΔEx3/WT expression ratio could potentially be used in risk classification for pediatric B-cell ALL.

摘要

生存素参与细胞凋亡的抑制及细胞分裂的调控。除野生型生存素(survivin-wt)外,至少已鉴定出四种具有不同功能的剪接变体(ΔEx3和3B具有抗凋亡功能,2α和2B具有促凋亡功能)。生存素在包括血液系统恶性肿瘤在内的多种癌症中高表达。虽然急性淋巴细胞白血病(ALL)是儿童中最常见的恶性肿瘤,但研究ALL中生存素表达的研究有限,且尚无关于ALL中3B和2α表达的研究。因此,我们对儿童B细胞ALL患者中survivin-wt及其剪接变体的表达进行了研究。通过定量实时聚合酶链反应对35例儿童B细胞ALL患者存档RNA样本中survivin-wt及其四种剪接变体的表达进行了研究。根据年龄、白细胞计数、髓外受累情况和遗传风险因素将患者分为高危组和标准风险组;比较这两个风险组之间生存素变体的表达。我们发现低风险组中survivin-ΔEx‌‍3/野生型(WT)表达的比值高于高风险组。高危和低危B细胞ALL组之间的比较分析表明,survivin-ΔEx3/WT表达比值可能用于儿童B细胞ALL的风险分类。

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