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目的:研究多药耐药基因(MDR1)、多药耐药相关蛋白基因(MRP)和调控细胞凋亡有重要作用的基因(bcl-2)在急性白血病(AL)中的表达以及它们与临床耐药之间的关系。方法:采用地高辛掺入的半定量逆转录聚合酶链反应(RT-PCR)及常规RT-PCR方法检测了54例急性白血病患者和10例正常人骨髓单核细胞中基因的表达情况。结果:54例AL中MDR1/MRP/bcl-2三基因表达阳性率为16.7%(9/54),MDR1/MRP/bcl-2三基因表达均阴性,发生频率为46.3%(25/54)。46例资料完整的白血病患者中三基因表达均阴性者80.0%缓解(CR),MDR1/MRP或MDR1/MRP/bcl-2共表达者无1人CR(P<0.01)。单基因分析表明MDR1、MRP、bcl-2基因表达阳性率分别为28.3%、41.3%和47.8%,其中MDR1阳性者CR率7.7%,明显低于MDR1阴性者CR率72.7%(P<0.01);MRP阳性CR率21.1%,明显低于阴性CR率77.8%(P<0.01);bcl-2阳性CR率36.4%,亦低于阴性CR率70.8%(P<0.05)。结论:MDR1/MRP或MDR1/MRP/bcl-2共表达的患者不易获得CR,白血病患者的耐药除了与MDR1高表达密切相关外,还与非P-糖蛋白(P-gp)介导的MRP及bcl-2表达等因素相关。
Objective: To investigate the expression of multidrug resistance gene (MDR1), multidrug resistance-related protein (MRP) gene and bcl-2 gene in acute leukemia (AL) and their relationship with clinical The relationship between drug resistance. Methods: The gene expression of bone marrow mononuclear cells from 54 patients with acute leukemia and 10 normal controls was detected by semi-quantitative reverse transcription-polymerase chain reaction (RT-PCR) and conventional RT-PCR. Results: The positive rate of MDR1 / MRP / bcl-2 gene in 54 AL patients was 16.7% (9/54), and the negative expression rates of MDR1 / MRP / bcl-2 genes were 46.3% . Among 46 patients with complete leukemia, 80.0% of patients with CR (CR) were negative, and none of CRR1 / MRP or MDR1 / MRP / bcl-2 had CR (P <0.01). The single gene analysis showed that the positive rates of MDR1, MRP and bcl-2 gene expression were 28.3%, 41.3% and 47.8%, respectively. The CR rate of MDR1 positive patients was 7.7%, significantly lower than that of MDR1 negative patients (72.7%, P <0.01) ; The MR positive CR rate was 21.1%, significantly lower than the negative CR rate 77.8% (P <0.01); bcl-2 positive CR rate was 36.4%, also lower than the negative CR rate 70.8% (P <0.05). CONCLUSIONS: Patients with MDR1 / MRP or MDR1 / MRP / bcl-2 co-expression are not readily available for CR. In addition to their close association with MDR1 overexpression, drug resistance in patients with leukemia is also associated with non-P-glycoprotein MRP and bcl-2 expression and other factors.