急性白血病患者bcl-2和bax基因表达的临床意义及其与mdr-1基因表达的关系

Clinic Significance of Expression of bcl-2 and bax Gene in Patients with Acute Leukemia and its Relationship with mdr-1 Gene Expression

细胞凋亡受抑作为肿瘤细胞的耐药机制 ,是急性白血病 (AL)预后不良的原因之一。bcl 2家族是目前最受重视的调控细胞凋亡的基因家族 ,本研究为探讨bcl 2和bax基因在急性白血病表达的意义 ,应用逆转录 聚合酶链反应 (RT PCR)方法测定 70例初治AL患者及 2 0例正常人的bcl 2 ,bax ,mdr 1基因mRNA水平的表达 ,用流式细胞术检测其蛋白表达。结果表明 ,bcl 2和bax基因在AL患者广泛表达 ,bcl 2mRNA平均表达水平明显高于正常对照 (1.4 6vs 0 .71,P <0 .0 5 )。bcl 2和bax基因表达及bax bcl 2比值与AL患者的年龄、性别、血小板计数、血红蛋白水平、骨髓原始细胞百分率、FAB分型和S +G2 M %均未发现相关。Bcl 2蛋白表达 (34.6 %vs 6 9.2 %,P <0 .0 5 ) ,bax bcl 2mRNA比值 (37.1%vs 82 .9%,P <0 .0 1)决定AL对化疗的敏感性 ,与ALCR率密切相关。bax bcl 2mRNA比值还是影响总生存期的因素。bcl 2与bax基因表达和mdr 1表达两者无相关关系。

It is generally accepted that the inhibition of apoptosis is one of the mechanism of drug resistance to tumor. Members of the bcl-2 gene family are the most important regulators in apoptosis. The purpose of this study is to evaluate the value of expression of bcl-2 and bax gene in predicting the prognosis of acute leukemia patients, and to explore the relationship between bcl-2 and bax expression and drug resistance. Seventy patients with acute leukemia entered this study. Expressions of bcl-2, bax and mdr-1 gene were measured by RT-PCR method and FCM. The result showed that: bcl-2 had been widely detected in specimens of blood or bone marrow from acute leukemia patients, the expression levels were much higher than those in normal control (1.46 vs 0.71, P< 0.05), bax expression levels and bax/bcl-2 ratio in patients had no significant difference with the control. No relationships were found between the expression levels of bcl-2 and bax and AL patients′ age, sex, platelet counts, hemoglobin levels, percentage of marrow blasts, FAB classification, and S+G 2M%. Both Bcl-2 protein expression (34.6% vs 69.2%, P<0.03) and bax/bcl-2 mRNA ratio(37.1% vs 82.9%, P<0.01) were associated with response to therapy and CR rate, bax/bcl-2 ratio also influences the overall survival time. There was no relationship between bcl-2 and bax expression levels and mdr-1 expression levels.