多药耐药功能实验对急性白血病化疗疗效的预测意义

Significance of Functional Assay of Multidrug Resistance for Prediction of Chemotherapy Outcomes in Acute Leukemia

背景与目的:多药耐药排药蛋白P-糖蛋白(P-glycoprotein,P-gp)在介导急性白血病多药耐药中的作用已得到公认。多项研究显示,P-gp及其编码基因MDR1mRNA的表达与白血病化疗疗效相关,但我们在临床实践中所获得的结果却并非如此。近年来多项研究发现,多药耐药功能实验结果比P-gp的表达水平对预测化疗疗效更有价值。为了解P-gp的表达和多药耐药功能实验对判断患者预后的价值,我们对24例初诊未治急性白血病患者白血病细胞膜P-gp的表达以及功能活性进行了检测,以探讨多药耐药功能试验对化疗疗效的预测价值。方法:用流式细胞仪测定24例急性白血病患者白血病细胞的P-gp表达率以及反映MDR功能的Rh123排出实验和细胞内柔红霉素蓄积实验的MIR值,并就患者的化疗疗效进行分组比较和相关分析。结果:CR患者初诊时白血病细胞P-gp表达率为(2.16±2.42)%,与NR患者犤(15.02±25.88)%犦差异无显著性(P=0.114)。CR患者初诊时白血病细胞Rh123排出实验的MIR值:MIR(RE)(1.16±0.38)明显低于NR患者(1.43±0.26)(P=0.045)。CR患者初诊时白血病细胞内柔红霉素积蓄实验的MIR值:MIR(IDA)(1.02±0.05)亦明显低于NR患者(1.47±0.44)(P=0.005)。MIR(RE)(r=0.590,P=0.006)和MIR(IDA)(r=0.867,P=0.000)与疗效间有显著相关性。P-gp表达率与疗?

BACKGROUND &OBJECTIVE:It is well known that the multidrug resistance (MDR) efflux protein, P glycoprotein (P gp), plays an important role in mediating MDR in acute leukemia. Several studies have shown that the expression level of P gp and its encoding gene MDR1 mRNA level are associated with the response of chemotherapy. But what we have observed in clinical practice is in contradiction with this. Besides, several recent reports have shown that the results of MDR functional assay are more predictive of chemotherapy outcomes than P gp expression level. To examine the prognostic value of P gp expression and MDR functional assay in acute leukemia, the authors determined the expression levels of P gp and MDR function in 24 patients with de novo acute leukemia. The predictive value of MDR functional assay for chemotherapy outcomes was discussed. METHODS: The expression percentile of P gp and the mean fluorescence intensity ratio of rhodamine 123 efflux assay and intracellular daunorubicin accumulation assay of patientsleukemic cell samples were determined with flow cytometry. The results of remission (CR) and non remission (NR) patients were compared. Correlative analysis was made between test results and chemotherapy outcomes. RESULTS: The expression levels of P gp were not significantly different between CR and NR patients (2.16%±2.42%versus 15.02%±25.88%, P=0.114). But the MIR (RE) (1.16±0.38 versus 1.43±0.26,P=0.045) and MIR (IDA)(1.02±0.05 versus 1.47±0.44,P=0.005) were both significantly lower in CR patients than those in NR patients. Both MIR (RE)(r=0.590,P=0.006) and MIR (IDA)(r=0.867,P=0.000) were significantly correlated with chemotherapy outcomes. But the expression level of P gp was not correlated with the chemotherapy results. CONCLUSION: The determination of MIR value of MDR functional assay is more valuable than P gp expression level in predicting chemotherapy outcomes.