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目的探讨ALL患儿Bim及c-Myc蛋白表达水平与糖皮质激素(GC)敏感性的关系,研究Bim表达水平是否可作为判断早期GC敏感性的客观指标,从而指导临床治疗和判断预后。方法采用Western blot方法检测1μmol·L-1地塞米松作用于人T-ALLGC敏感细胞株(CEM-C7)和GC耐药细胞珠(CEM-C1)0 h、12 h、24 h、36 h、48 h及72 h后Bim和c-Myc蛋白表达的变化;以30例初诊ALL患儿为研究对象,采用Western blot分析ALL患儿GC诱导前、GC诱导后24 h、48 h、72 h以及第8天Bim蛋白表达情况,探讨Bim表达水平与ALL患儿GC敏感性的关系。结果地塞米松作用CEM-C7后12 h Bim表达量开始增加,直到72 h仍维持在较高水平,c-Myc表达水平在地塞米松作用后24 h明显下降,到72 h降至最低,而在GC耐药细胞CEM-C1中Bim和c-Myc表达水平均无变化。30例初诊ALL患儿,25例GC敏感,5例GC不敏感,Bim表达水平在GC敏感组GC诱导前及诱导后24 h均高于GC不敏感组,差异均有统计学意义(Pa<0.05),但在GC诱导后48 h、72 h及第8天,2组Bim表达水平比较差异均无统计学意义。GC敏感组诱导后不同时间点未发现Bim表达呈增高趋势。结论 GC通过上调Bim表达及抑制c-Myc的表达,而诱导ALL细胞凋亡;Bim有可能作为判断ALL患儿早期GC敏感与否的客观指标,从而指导临床治疗及判断预后。
Objective To investigate the relationship between the expression of Bim and c-Myc in patients with ALL and the sensitivity of glucocorticoid (GC), and to investigate whether Bim expression can be used as an objective indicator of early GC sensitivity to guide clinical treatment and prognosis. Methods Western blotting was used to detect the effect of 1μmol·L-1 dexamethasone on C-T-ALLGC sensitive cell line (CEM-C7) and GC-resistant cell beads (CEM-C1) , 48 h and 72 h after BMSCs were harvested. The changes of Bim and c-Myc protein expression in 30 newly diagnosed ALL children were investigated by Western blot. And Bim protein expression on the 8th day to explore the relationship between Bim expression and GC sensitivity in children with ALL. Results The expression of Bim at 12 h after dexamethasone treatment began to increase, and remained high until 72 h. The expression of c-Myc decreased significantly 24 h after dexamethasone treatment and reached the lowest level at 72 h. However, there was no change in the expression of Bim and c-Myc in GC-resistant cells CEM-C1. In 30 newly diagnosed ALL children, 25 cases were sensitive to GC and 5 cases were not sensitive to GC. The expression level of Bim in GC-sensitive group was higher than that in GC-sensitive group before and 24 h after GC induction (P < 0.05). However, there was no significant difference in Bim expression between the two groups at 48 h, 72 h and 8 d after GC induction. Bim expression was not found to be increased at different time points after GC induction. Conclusion GC can induce the apoptosis of ALL cells by up-regulating the expression of Bim and inhibiting the expression of c-Myc. Bim may be used as an objective indicator of early GC sensitivity in children with ALL, guiding the clinical treatment and prognosis.