mdr-1基因在淋巴瘤组织中的表达与临床意义

Expression and Clinical Significan ce of mdr-1Gene in Lymphoma

背景与目的:多药耐药是一种常见的化疗耐药现象。mdr-1是产生多药耐药的编码基因之一,其表达与复发淋巴瘤多药耐药性的相关性目前尚未明确。在对mdr-1表达水平与淋巴瘤疗效的相关性研究方面,未取得一致结论。本文旨在检测淋巴瘤组织P-gp及mdr-1mRNA表达水平,并初步观察淋巴瘤P-gp表达水平与近期化疗疗效的关系。方法:使用流式细胞术检测31例初治与复发淋巴瘤P-gp表达水平,观察其中17例淋巴瘤P-gp表达水平与近期化疗疗效的关系。同时使用荧光定量RT-PCR技术检测淋巴瘤mdr-1mRNA表达水平。结果:19%(4/21)初治淋巴瘤P-gp高表达;60%(6/10)复发淋巴瘤P-gp高表达。复发淋巴瘤P-gp高表达率高于初治淋巴瘤(P=0.012)。46%(6/13)P-gp低表达或不表达病例化疗后完全缓解;仅25%(1/4)P-gp高表达病例化疗后完全缓解。非P-gp高表达组化疗完全缓解率较P-gp高表达组增高21%(P=0.6)。荧光定量RT-PCR检测18例初治淋巴瘤mdr-1mRNA含量为4.00×102～1.32×104copies/μgRNA;10例复发淋巴瘤mdr-1mRNA含量为4×102～4×104copies/μgRNA。复发淋巴瘤的mdr-1mRNA含量高于初治淋巴瘤(P<0.05)。结论:复发淋巴瘤组织过度表达P-gp及mdr-1mRNA;本实验中淋巴瘤P-gp表达水平与近期化疗疗效的相关性尚不明显。

Background &Objective:It is still unclear whether overexpr ession of mdr-1gene play a role in the chemotherapy resistance of lymphom a.This study was designed to investigate P-glycoprotein(P-gp)and mdr-1mRNA levels of lymphoma and to observe the impact of P-gp level upon chemotherapy resp onse.Methods :Ten samples of relapsed lymphoma and 21samples of untreated lymphoma were assessed by flow cytom etry(FCM).The mdr-1mRNA levels were determined by real-time reverse-tr anscription PCR assay simultaneously in eighteen samples.The impact of P-gp levels upon chemotherapy response was observed in seventeen patients.Results:Nineteen Percent (4/21)patients overexpressed P-gp at diagnosis as compared to 60%(6/10)in relapse(P=0.012).The copy numbers of mdr-1mRNA were 4×10 2 -1.32×10 4 copies /μgRNA in untreated group and 4×10 2 -4×10 4 copies /μgRNA in recurrent group.There existed significant difference in the distribution of md r-1mRNA expression between these tw o groups,P<0.05.The complete response rates were 46%(6/13)in P-gp non-overexpression group an d 25%(1/4)in P-gp overexpression group(P=0.60).Conclusion:Relapsed lymphomas highly express P-gp and mdr-1mRNA.The overexpression of mdr-1gene may pla y a role in the multidrug resistance of relapsed lymphoma.