儿童T细胞型急性淋巴细胞白血病中NOTCH1基因突变的特征及临床意义研究  

The characteristics and clinical significance of NOTCH1 mutations in childhood T-cell acute lymphoblastic leukemia

作　　者：闫慧[1,2] 刘兰波[1,2] 丁丽霞[1,2] 李本尚[1,3] 沈树红[1,3] 汤静燕[1,3] 莫茜[1,2] 

机构地区：[1]上海交通大学医学院附属上海儿童医学中心卫生部儿童血液肿瘤重点实验室,上海200127 [2]上海交通大学医学院附属上海儿童医学中心儿科转化医学研究所,上海200127 [3]上海交通大学医学院附属上海儿童医学中心血液肿瘤科,上海200127

出　　处：《临床儿科杂志》2015年第10期870-875,共6页Journal of Clinical Pediatrics

基　　金：上海交通大学上海市教委东方学者计划(No.2012-66);上海市科委生物医药处重点项目子项目(No.13431900502);上海交通大学医工交叉基金(No.YG2012MS01)

摘　　要：目的阐明NOTCH1基因突变在儿童T细胞型急性淋巴细胞白血病(T-ALL)中的特征及临床意义。方法通过对28例T-ALL患儿NOTCH1基因的异二聚体(HD)区及脯氨酸-谷氨酸-丝氨酸-苏氨酸(PEST)区测序,研究T-ALL患儿中NOTCH1基因突变的发生率、位点、类型及其与预后的相关性。结果 28例T-ALL患儿中,15例(51.57%)患儿的NOTCH1基因发生突变,均为杂合性突变。突变患儿入院时外周幼稚淋巴细胞比例及骨髓幼稚细胞比例与无突变患儿相比均明显升高(P<0.05)。28例患儿的一年缓解率为75.0%(21/28),其中突变患儿的一年缓解率为80.0%(12/15),无突变患儿为69.2%(9/13)。此外,3例复发的突变组患儿至一年随访时均已死亡(一年时病死率为20%),而4例复发的无突变患儿经再次化疗后至一年随访时均存活(一年时病死率为0%)。结论儿童T-ALL患者中NOTCH1基因突变发生率高、位点多样;NOTCH1突变者初诊时疾病更严重,短期预后较好、而复发后挽救治疗预后更差的趋势。Objective To clarify the characteristics and clinical significance of the NOTCH1 mutations in childhood T-cell acute lymphoblastic leukemia（T-ALL）. Methods Amplify and sequence the heterodimerization（HD） domain and the proline-glutamicacid-serine-threonine（PEST） domain of the NOTCH1 gene in 28 T-ALL children, in order to explore the frequency, position and type of the mutations as well as their reletions with prognosis. Results In 28 children with T-ALL, 15 cases（51.57%） had been identified the NOTCH1 mutations, all of which were heterozygous mutations. The lymphoblast counts in peripheral blood and bone marrow in the NOTCH1 mutant group at admission were significantly higher than in the non-mutant group（P0.05）. The 1-year remission rate in the 28 children with T-ALL was 75%（21/28）, including 80%（12/15） in mutant group in which 3 patients relapsed and all of them died（1-year mortality 20%） and 69.20%（9/13） in non-mutant group in which 4 patients relapsed but all survived（1-year mortality 0%）. Conclusions The children with T-ALL had a high incidence of NOTCH1 mutations at various sites. In addition, the patients with NOTCH1 mutations had more severe disease at diagnosis, better short-term prognosis and poor outcome with salvage therapy after relapse.

关 键 词：T细胞型急性淋巴细胞白血病 NOTCH1基因 儿童 

分 类 号：R733.71[医药卫生—肿瘤]