P-糖蛋白与乳腺癌耐药蛋白基因在急性髓系白血病中表达的意义

Clinical Significance of Expressions of P-glycoprotein and the Breast Cancer Resistance Protein Gene in Acute Myeloblastic Leukemia

目的:探讨多药耐药蛋白(P-gp)和乳腺癌耐药蛋白(BCRP)基因在急性髓系白血病(AML)中的表达以及它们的相关性。方法:本研究应用半定量逆转录-聚合酶链式反应(RT-PCR)的方法,以β-actin作为内对照,检测41例AML患者及20例非恶性血液病对照组的骨髓白细胞的BCRP mRNA表达;应用流式细胞仪(FCM)采用直接免疫荧光标记法对41例AML患者及20例正常对照的骨髓单个核细胞(BMMNC)进行P-gp检测。结果:(1)AML中P-gp总阳性率与正常对照组无显著性差异(P>0.05);BCRP基因总阳性率明显高于正常对照组(P<0.05)。(2)AML中P-gp难治/复发组阳性率明显高于初治组(P<0.05);AML中BCRP基因难治/复发组阳性率与初治组无显著差异(P>0.05)。(3)P-gp+组完全缓解(CR)率和BCRP+组CR率明显低于P-gp-组和BCRP-组(P<0.05)。P-gp+组和BCRP+组早期复发率明显高于P-gp-组和BCRP-组(P<0.05)。(4)P-gp+/BCRP+组CR率明显低于P-gp-/BCRP-组(P<0.01);P-gp+/BCRP+组早期复发率明显高于P-gp-/BCRP-组(P<0.05)。(5)P-gp和BCRP基因在初治组和难治/复发组表达不相关(P>0.05)。结论:(1)P-gp和BCRP基因均与临床耐药密切相关。(2)P-gp和BCRP基因高表达均提示预后不良。联合检测P-gp和BCRP基因对评价AML的预后有较大意义。(3)P-gp和BCRP基因表达无相关性。

Objective：To investigate the relationship between the expressions of P-glycoprotein（P-gp） and the breast cancer resistance protein （BCRP） gene in acute myeloblastic leukemia（AML）. Methods： （1）Using semi-quantitative reverse transcription polymerase chain reaction（RT-PCR） assay andβ-actin as positive reference , we detected the expressions of BCRP gene in 41 AML samples and 20 patients with non-malignance hematology disease as a control group. The expression rate of P-gp in bone marrow mononuclear cells（BMMNC） from 41 AML sample and 20 normal controls were detected by flow cytometry with direct immunofluorescent labeling. Results： （1） The results showed that there were no significant difference between the positive percentage of P- gp in AML and that of normal control group（P〉0.05）; The positive percentage of BCRP gene expression in AML was higher than that of normal control group（P〈0.05）. （2）The positive percentage of P-gp was expressed higher at relapsed/refractory group as compared to diagnosis group （P〈0.05）,but there were no significant difference in the positive percentage of BCRP gene expressed patients at relapsed/refractory group as compared to diagnosis group（P〉0.05）. （3） The complete remission （CR）rate in patients with P-gp^＋ and BCRP^＋ were lower than that in patients with P-gp^- and BCRP^-（P〈0.05）;The early relapse rates of patients with P-gp＋ and BCRP＋ were higher than that in patients with P-gp^- and BCRP^- （P〈0.05）. （4） Compared with patients with P-gp^-/BCRP^- ,The patients with P-gp^＋/BCRP^＋ were characteristic of lower CR rate and early relapse rates（P〈0.01;P〈0.05）. （5）No significant correlation between P-gp and BCRP was found by linear regression analysis at relapsed/refractory group as compared to diagnosis group （P〉0.05）. Conclusions.（1）Clinical resistance to chemotherapy in AML is closely associated with expression of P-gp and BCRP. （2）High expression of P-gp and BCRP is adverse prognosis factors in de novo AML. Evaluation of P-gp and BCRP co-expression play an important role in AML. （3）The correlation between P-gp and BCRP was not found.