成人急性白血病患者细胞周期蛋白A基因表达与耐药的关系

The correlation of cyclin A gene expression with drug resistance in adult acute leukemia patients

目的 探讨细胞周期蛋白A(cyclinA)基因在成人急性白血病 (AL)患者中的表达以及与耐药的关系。方法 采用半定量RT PCR技术对 32例多药耐药和 32例化疗敏感的AL患者和 2 0名正常人进行细胞周期蛋白A、mdr1、TopoⅡα、bcl 2mRNA水平的测定。结果 耐药组患者细胞周期蛋白A及TopoⅡαmRNA的表达水平均明显低于敏感组患者 (P <0 .0 1 ) ,2 0名正常人在同一实验条件下未检出细胞周期蛋白AmRNA的表达 ;耐药组患者mdrl及bcl 2mRNA表达水平均明显高于敏感组 (P <0 0 1 ) ;64例AL患者中 ,细胞周期蛋白A与TopoⅡα表达水平呈高度的正相关 (r =0 .794,P =0 .0 0 0 ) ;细胞周期蛋白A与TopoⅡα同时阳性低表达的 1 0例AL患者全部耐药 ;经Binary逻辑回归分析显示细胞周期蛋白A与耐药显著相关。结论 细胞周期蛋白A可能会成为判断AL患者预后的新指标 ,联合TopoⅡα检测对判断AL耐药有意义。

Objective To investigate the relationship between the expression of cyclin A and drug resistance in patients with adult acute leukemias. Methods The mRNA expressions of cyclin A,mdr1,TopoⅡα and bcl 2 were measured in 64 patients with adult acute leukemia (AL) and 20 normal subjects by semi quantitative reverse transcriptase polymerase chain reaction (RT PCR). Results ①The cyclin A and TopoⅡα mRNA expression levels in the treatment resistant group were significantly lower than that in the sensitive group (P<0.01). There was no cyclin A mRNA expression in the 20 normal subjects under the same experiment condition. ②The mdr1 and bcl 2 mRNA expression levels in the resistant group were significantly higher than that in sensitive group (P<0 01). ③Cyclin A and TopoⅡα gene expression levels were positively correlated (r=0.794, P=0.000)in the 64 AL patients, and there was a negative correlation between the gene expression levels of cyclin A and mdr1(r=-0 337, P=0.029) in the drug resistant group. ④Ten AL patients with low expressions of both cyclin A and TopoⅡα were all in the resistant group. Logistic regression of binary analysis showed a significant correlation between the low expression of cyclin A and drug resistance. Conclusion Low expression of cyclin A gene might be a unfavorable prognostic factor for patients with AL and measurement of both cyclin A and TopoⅡα gene expression would predict drug resistance for AL patients.