白血病细胞凋亡与bcl-2和bax-alpha表达的研究

APOPTOSIS AND EXPRESSION OF bcl-2 and bax alpha PROTEINS IN ACUTE LEUKEMIA CELLS

目的 研究白血病细胞细胞凋亡率与 bcl- 2和bax- alpha阳性率及表达水平关系。方法 选择难治或复发的化疗耐药白血病患者和初治化疗敏感白血病患者各 10例 ,分离白血病细胞 ,柔红霉素 (5 0 0 ng/ ml)诱导凋亡 ,应用流式细胞术比较分析耐药组和敏感组白血病细胞的凋亡率与 bcl- 2和 bax- alpha阳性率和表达水平的关系。结果 化疗耐药组和化疗敏感组对柔红霉素诱导的凋亡率有显著差异 ,敏感组 (2 3.2 6 %± 12 .94% )显著高于耐药组 (2 .2 6 %± 1.44 % ) ,(P=0 .0 0 1) ;耐药组白血病细胞凋亡率与 bcl- 2阳性率呈负相关 (r=- 0 .6 47,P=0 .0 43) ,与 bax- alpha阳性率和相对荧光强度呈正相关 (r=0 .883,P=0 .0 0 1;r=0 .814,P=0 .0 0 4)及 bcl- 2 :bax- alpha比率呈负相关 (r=-0 .893,P=0 .0 0 1) ;敏感组凋亡率 bax- alpha的阳性率和荧光强度呈正相关 (r=0 .6 5 3,P=0 .0 41,r=0 .76 2 ,P=0 .0 10 ) ,与 bcl- 2 :bax- alpha比率呈负相关 (r=- 0 .741,P=0 .0 14)。结论 白血病细胞耐药性与细胞的凋亡抗性有关 ,这种凋亡抗性与 bcl- 2和 bax- alpha的表达比例增高有关 ,特别是 bax-

Objective To study the correlation of the cell apoptotic rate and the levels of bcl 2 and bax alpha expression in leukemia patients.Methods The patients were divided into two groups:10 cases with chemo resistant leukemie(refractory or relapsed leukemia) and 10 cases with chemosensitive leukemia (primary treated sensitive leukemia). Apoptotic reates of leukemia cells of both groups were detected by flow cytometry DNA quntitative assay with PⅠ staine, which were induced with Daunorubicin (DNR 500 mg/ml).Multiparameter flow cyto metry measured the percentages and intensities of bcl2 and bax alpha expression of leukemia cells of both groups.Results The daunorubicin induced apoptotic rates were significantly different between chemosensitive and chemoresistant groups ( P =0 001). The apoptosis of chemoresistant leukemia cells had correlation with percentage of bcl 2 positive cells (r=-0 647, P =0 043) and with percentage and level of bax alpha expression (r=0 883, P =0 001;r=0 814, P =0 04),and also with bcl 2/bax alpha ratio(r=0 893, P =0 001) The apoptosis of chemosensitive cells was correlated with the positive percentage and level of bax alpha expression (r=0 653 P =0 041; r=0 762, P =0 010), and with the bcl 2:bax alpha ratio (r=0 741, P =0 014).Conclusion The chemoresponse of both drug resistant group and drug sensitive groups of leukemia patients is associated with the apoptosis of leukemia cells induced by DNR which correlated with the bcl 2:bax alpha ratio,especially with the bax alpha expression.