MDR基因异常表达与淋巴系统恶性肿瘤化疗反应的相关性  

The relationship between abnormal MDR gene expression and chemotherapy response in lymphoid malignancies

作　　者：徐迎春[1] 林玉梅[2] 张凤春[1] 

机构地区：[1]上海交通大学医学院附属仁济医院肿瘤中心,上海200127 [2]吉林大学中日联谊医院血液肿瘤科

出　　处：《中华肿瘤杂志》2006年第5期353-356,共4页Chinese Journal of Oncology

摘　　要：目的探讨淋巴性恶性肿瘤多药耐药-1(MDR1)、拓扑异构酶Ⅱ(Topo Ⅱ)及糖皮质激素受体(GCR)基因表达与肿瘤复发和化疗反应的关系。方法应用RT-PCR、狭线杂交、配体标记方法,检测189例淋巴性恶性肿瘤患者的MDR、TopoⅡ和GCR基因表达。结果 (1)MDR、TopoⅡ、 GCR基因在初治和复发难治的ALL、NHL、NHL-L和MM患者中有不同程度的异常表达,以复发难治组为著。(2)MDR1高表达(MDR1+)组患者CR率均显著低于MDR1表达阴性(MDR1-)组(P< 0．05),MDR1+组患者复发率均显著高于MDR1-组(P<0．05)。初治TopoⅡ低表达(TopoⅡ-)组患者复发率显著高于TopoⅡ高表达(TopoⅡ+)组(P<0．05),复发难治TopoⅡ-组患者CR率显著低于 TopoⅡ+组(P<0．05)。GCR位点低表达(GCR-)组患者CR率均显著低于GCR位点正常表达组 (P<0．05)。(3)单因素耐药机制中,以MDR1+组CR率最低,TopoⅡ-组次之,GCR减低组最高。多重耐药机制共存时,MDR1++TopoⅡ-+GCR-组及MDR1++TopoⅡ-组患者CR率(11．1％和 15．4％)分别显著低于MDR1+组、TopoⅡ-组和GCR-组(36．7％、48．0％和53．8％;P<0．05-P< 0．001)。结论淋巴系统恶性肿瘤存在原、继发耐药,MDR1高表达、TopoⅡ和GCR低表达与患者化疗CR率降低和2年复发率升高有关,多重耐药机制联合分析对淋巴系统恶性肿瘤的化疗反应和预后判断具有重要意义。Objective To investigate the expression of muhidrug resistance-1 （MDR1 ）, Topoisomerase Ⅱ （Topo Ⅱ ） , glucocorticoid receptor （ GCR ） and their correlation with relapse rate and chemotherapy response in lymphoid malignancies. Methods The expression of MDR1 , Topo Ⅱ and GCR in 189 patients with lymphoid neoplasms was examined by RT-PCR, slot blot and ligand-labeUed methods. Results （ 1 ） The expressions of MDR2 , Topo Ⅱ , GCR in untreated and relapsed/refractory patients with ALL, NHL, NHL-L, MM were significantly abnormal at varying levels, especially in the relapsed/refractory group. （2）The complete remission （CR） rate of MDRt high expression group （MDR1^＋ ） was significantly lower than that of MDR1 negative expression （ MDR1^-） group （ P 〈 0.05 ） , and the relapse rate of MDR^1＋ group was significantly higher than that of MDR1 group （P 〈0.05 ）. In untreated patients, the relapse rate in the Topo Ⅱ low expression （ Topo Ⅱ^ - ） group was positively higher than Topo Ⅱ high expression （ Topo Ⅱ^＋ ） group（P 〈0. 05）, whereas in the relapsed/refractory patients, the CR rate of Topo Ⅱ^- group was significantly lower than that of Topo II ^＋ group （ P 〈 0. 05 ）. In the untreated and relapsed/refractory patients, the CR rates of low GCR expression （ GCR^- ） group was obviously lower than that in the normal GCR expression group（ P 〈 0.05）. （3） Considering mono-drug resistance mechanism, CR rate of MDR（ group was the lowest, Topo Ⅱ^- group took the second place and GCR^- group was the highest. As multiple drug resistance mechanisms coexisted, the CR rate of MDR1^ ＋ Topo Ⅱ^ - ＋ GCR^- group and MDR1^ ＋ Topo Ⅱ^- group （ 11.1% and 15.4% , respectively） were significantly lower than that of MDR1^＋, TopoⅡ^- and GCR^- group （36.7%, 48.0% and 53.8%, respectively; P 〈0.05 -P 〈0.001）. Condusion There are primary and acquired drug resistance in lymphoid neoplasms. The high expression of MDRI, low express

关 键 词：淋巴系统恶性肿瘤 多药耐药-1 拓扑异构酶Ⅱ 糖皮质激素受体 

分 类 号：R733[医药卫生—肿瘤]