Notch1蛋白表达在儿童急性B淋巴细胞白血病预后预测中的意义

Prognostic significance of Notch1 protein expression in children with pediatric B-cell acute lymphoblastic leukemia

目的研究Notch1蛋白在儿童急性B淋巴细胞白血病（B-ALL）中的表达及其对预后的影响。方法采用免疫组织化学（SABC）法检测初诊的63例B-ALL、14例T系ALL（T-ALL）及34例非恶性血液病患儿（对照组）骨髓白血病细胞中Notch1蛋白表达；反转录聚合酶链反应（RT-PCR）法检测ALL患儿中NotchlmRNA表达。结果Notchl蛋白在T—ALL及B—ALL中有异常高表达，分别为71．4％和31．7％，与对照组（8．8％）比较差异有统计学意义（P〈0．001、0．05）。多因素分析显示：Notchl蛋白在B—ALL中的表达与患儿初诊时的性别、年龄、外周血白细胞数均无相关性（P均〉0．05），也与早期治疗反应无关。然而，长期治疗效果经Kaplan．Meier分析表明：Notchl蛋白阴性组患儿长期无病生存率高达92．7％，而Notch1蛋白阳性组患儿长期无病生存率仅为54．5％（P=0．0054）。结论儿童B．ALL中Noteh1蛋白的阳性表达可能是预后不良的指标，干预Notch1信号传导通路有望成为治疗此部分患儿分子靶向治疗的新靶点。

Objective To investigate Notchl protein expression of leukemic ceils in children with pediatric B- cell acute lymphoblastic leukemia（B-ALL） and its effect on prognosis. Methods The expression of Notchl protein of leukemic cells in bone marrow smears was detected by immunohistochemistry（SABC） in primarily diagnosed childhood ALL,including 63 cases of B-ALL and 14 cases of T-ALL, a group of 34 children with no malignancy served as con- trois. Reverse transcription-ploymerase chain reaction was used to assay Notchl mRNA expression in ALL patients. Re- sults The incidence of Notch1 expression was 31.7% in B-ALL patients,71.4% in T-ALL patients, and 8.8% in control group, respectively. Notchl protein was aberrantly expressed in both B-ALL and T-ALL compared with the controls （ P 〈 0.05, P 〈 0.001 ）. Multivariate analysis revealed that the expression of Notchl protein in B-ALL was not asso- ciated with patients＇ age, gender, WBC count at diagnosis （all P 〉 0.05 ）, it had no influence on the early treatment re- sponse. Nevertheless, the Kaplan-Meier curve of event-free survival showed that, in the patients without Notchl protein expression, the long-term event-free survival rate was as high as 92.7%, in contrast, in the children with Notchl expres- sion,the event-free survival was only 54.5% （P =0.0054）. Conclusions The expression of Notchl protein in pediat- ric B-ALL may predict a poor prognosis,and interfering with Notchl signaling could be employed as a potential thera- peutic target for those patients with Notchl expression.