摘要
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 levels of Bim,c-Myc and the sensitivity of glucocorticoids（GC） in children with acute lymphoblastic leukemia（ALL）,and to further address whether the expressions of Bim could be served as an objective index for GC sensitivity to guide clinical treatment and predict prognosis.Methods Western blot analysis was performed to detect the levels of Bim and c-Myc in childhood T-ALL GC-resistant cell line（CEM-C1） and T-ALL GC-sensitive cell line（CEM-C7） treated with 1 μmol·L-1 dexamethasone in different time intervals（0 h,12 h,24 h,36 h,48 h and 72 h）.Bim expression pattern was further studied in 30 newly diagnosed childhood ALL samples.Results In CEM-C7,Bim expression increased at 12 h after dexamethasone treatment and it remained at a high level until 72 h,and c-Myc expression decreased at 24 h after dexamethasone treatment and reached its lowest level after 72 h,whereas there was no changes in the expressions of Bim and c-Myc in GC-resistant CEM-C1 cells.In the 30 newly diagnosed ALL children,25 cases were clinically GC sensitive,5 cases were GC insensitive,and the Bim expression level in this group was higher than that in the GC-insensitive group both before the use of GC and after 24 h of treatment with GC,and the differences between the 2 groups were statistically significant（Pa0.05）.However,no differences in the expressions were found between 2 groups after 48 h,72 h and 7 days of dexa-methasone treatment.There was no trend of increasing the expression of Bim after 24 h of treatment in the GC-sensitive group.Conclusions GC induces the apoptosis of ALL cells by up-regulating Bim and inhibition of c-Myc expression.Bim expression can be used as an objective index to judge the GC sensitivity in children with ALL.
出处
《实用儿科临床杂志》
CAS
CSCD
北大核心
2011年第9期680-683,共4页
Journal of Applied Clinical Pediatrics
基金
国家自然科学基金(30973237)
