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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 relationship between the expression of multidrug resistance-1 (MDR1), topoisomerase Ⅱ (Topo Ⅱ) and glucocorticoid receptor (GCR) in lymphoid malignancies and tumor recurrence and chemotherapy. Methods RT-PCR, narrow-line hybridization and ligand labeling were used to detect the expression of MDR, TopoⅡand GCR in 189 patients with lymphoid malignancies. Results (1) MDR, Topo Ⅱ and GCR genes were abnormally expressed in ALL, NHL, NHL-L and MM patients who were refractory to relapse and relapse. (2) The CR rates of patients with MDR1 overexpression (MDR1 +) were significantly lower than those of patients with MDR1-negative (MDR1-) and those with MDR1 + (all P <0.05). 05). The recurrence rate was significantly higher in TopoⅡ- group than in TopoⅡ + group (P <0.05), and was significantly lower in TopoⅡ- group than in TopoⅡ + group (P < 0.05). The CR rate of GCR patients was significantly lower than that of GCR patients (P <0.05). (3) In the single factor drug resistance mechanism, the CR rate in MDR1 + group was the lowest, followed by TopoⅡ- and GCR decrease group. The CR rates (11.1% and 15.4%) in MDR1 ++ TopoⅡ- + GCR-group and MDR1 ++ TopoⅡ-group were significantly lower than those in MDR1 +, TopoⅡ- and GCR- (36.7%, 48.0% and 53.8%; P <0.05-P <0.001). CONCLUSIONS: The primary and secondary MDR1, the high expression of MDR1 and the low expression of TopoⅡ and GCR are associated with the decrease of CR rate and 2-year recurrence rate in patients with lymphatic system malignant tumor. The combination of multi-drug resistance mechanism and chemotherapy in the treatment of lymphatic system malignant tumor Response and prognostic judgment is of great significance.