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初发和复发儿童急性淋巴细胞白血病中多药耐药相关蛋白(MRP1)和肺耐药蛋白(LRP)的信使核糖核酸分析

Messenger RNA analysis of the multidrug resistance related protein (MRP1) and the lung resistance protein (LRP) in de novo and relapsed childhood acute lymphoblastic leukemia.

作者信息

Sauerbrey Axel, Voigt Astrid, Wittig Susann, Häfer Ralf, Zintl Felix

机构信息

Department of Pediatrics, University of Jena, Germany.

出版信息

Leuk Lymphoma. 2002 Apr;43(4):875-9. doi: 10.1080/10428190290017024.

Abstract

In this study, 86 children (58 initial ALL and 28 children with relapsed disease) were investigated for lung resistance protein (LRP) and multidrug resistance related protein (MRPI)-mRNA expression by semiquantitative RT-PCR. The majority of investigated cases demonstrated variable LRP and MRP1 mRNA expression, when normalized for beta-microglobulin expression. LRP and MRPI mRNA expression may be coordinately regulated, as expression of both transcripts was found to be significantly correlated (p = 0.0001). No differences of LRP and MRP expression were observed between initial and relapsed stage patients (LRP: p = 0.89 and for MRP: p = 0.09). The prognostic value of both resistance mechanisms was subjected to Kaplan-Meier analysis for event-free survival. For this analysis the patients were divided into groups with high or low LRP or MRPI mRNA expression by utilizing the median value as the cut-off point. Overexpression of both resistance mechanisms had no prognostic significance in our retrospective study (log-rank test for LRP: p = 0.12 and for MRPI: p = 0.95), however, patients who showed high LRP expression exhibited a lower tendency of remaining in continuous first remission.

摘要

在本研究中,通过半定量逆转录聚合酶链反应(RT-PCR)对86名儿童(58例初发急性淋巴细胞白血病(ALL)和28例复发疾病儿童)进行了肺耐药蛋白(LRP)和多药耐药相关蛋白(MRP1)-mRNA表达的研究。在以β-微球蛋白表达进行标准化后,大多数受调查病例显示LRP和MRP1 mRNA表达存在差异。LRP和MRP1 mRNA表达可能受到协同调节,因为发现两种转录本的表达显著相关(p = 0.0001)。初发期和复发期患者之间未观察到LRP和MRP表达的差异(LRP:p = 0.89,MRP:p = 0.09)。对这两种耐药机制的预后价值进行了Kaplan-Meier无事件生存分析。为此分析,利用中位数作为分界点将患者分为LRP或MRP1 mRNA高表达或低表达组。在我们的回顾性研究中,两种耐药机制的过表达均无预后意义(LRP的对数秩检验:p = 0.12,MRP1的对数秩检验:p = 0.95),然而,LRP表达高的患者维持首次持续缓解的趋势较低。

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