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[摘要]
目的 探讨难治性急性淋巴细胞白血病(ALL)患儿治疗效果与地塞米松治疗敏感性的关系及耐药机制。方法 回顾性分析榆林市第二医院自2015年1月-2017年7月治疗的105例难治性急性淋巴细胞白血病患儿临床资料,根据不同治疗敏感性分为敏感组与不敏感组。患儿均采取地塞米松治疗,剂量为7.5~10 mg/(m2·d),持续治疗7 d后,给予标准化疗方案。比较两组化疗第26天骨髓象、危险度分级及地塞米松治疗前后的外周血白细胞糖皮质激素受体(GR)蛋白、GRαmRNA、Bcl-2蛋白家族促凋亡因子Bin蛋白、Bin mRNA表达水平;随访6个月,比较两组完全缓解率、复发率、死亡率。结果 在105例难治性ALL患儿中,地塞米松治疗敏感69例、治疗不敏感36例。敏感组化疗第26天骨髓象分型、危险度分级均显著优于不敏感组,差异均有统计学意义(P<0.05)。敏感组地塞米松治疗后GR蛋白、GRα mRNA、Bin蛋白、BinmRNA表达水平均显著高于不敏感组,差异均有统计学意义(P<0.05)。敏感组完全缓解率显著大于不敏感组,复发率、死亡率均显著小于不敏感组,差异均有统计学意义(P<0.05)。结论 难治性ALL患儿GR表达水平上调可增强地塞米松治疗敏感性,放大地塞米松诱导细胞凋亡效应,对于提高近期疗效具有一定作用,值得进一步研究应用。
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[Abstract]
Objective To investigate the relationship between the therapeutic effect of dexamethasone and the sensitivity of dexamethasone in children with refractory acute lymphoblastic leukemia (ALL) and the mechanism of drug resistance. Methods The clinical data of 105 children with refractory ALL treated in Yulin NO. 2 Hospital from January 2015 to July 2017 were retrospectively analyzed, and divided into sensitive group and insensitive group according to the sensitivity of different treatments. All the children were treated with dexamethasone at a dose of 7.5-10 mg/(m2·d). After 7 days of continuous treatment, standardized treatment was given. Myelogram and risk grading on the 26th day of chemotherapy were compared between the two groups. And the glucocorticoid receptor (GR) protein, GRα mRNA, Bin protein, and Bin mRNA expression before and after dexamethasone treatment in peripheral blood were measured. After 6 months of follow-up, the complete remission rate, relapse rate, and mortality rate were compared between two groups. Results Among 105 children with refractory ALL, dexamethasone was sensitive to 69 patients and insensitive to 36 patients. On the 26th day after chemotherapy, the myelogram classification and risk grade of the sensitive group were significantly better than that of the insensitive group, and the differences were statistically significant (P<0.05). The expression of GR protein, GRα mRNA, Bin protein and Bin mRNA in the sensitive group after treatment with dexamethasone was significantly higher than that in the insensitive group (P<0.05). The complete remission rate in the sensitive group was significantly greater than that in the insensitive group, and the recurrence rate and mortality were significantly less than those in the insensitive group, differences were statistically significant (P<0.05). Conclusion Up-regulation of GR expression in children with refractory ALL may increase the sensitivity of dexamethasone treatment, amplify dexamethasoneinduced apoptosis, it has a role in improving the short-term curative effect, it is worth further research and application.
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