Sauerbrey Axel, Voigt Astrid, Wittig Susann, Häfer Ralf, Zintl Felix
Department of Pediatrics, University of Jena, Germany.
Leuk Lymphoma. 2002 Apr;43(4):875-9. doi: 10.1080/10428190290017024.
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.
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。