CAJ | 학술논문

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。
목적：천명NOTCH1기인돌변재인동T세포형급성림파세포백혈병（T-ALL）중적특정급림상의의。방법통과대28례T-ALL환인NOTCH1기인적이이취체（HD）구급포안산-곡안산-사안산-소안산（PEST）구측서，연구T-ALL환인중NOTCH1기인돌변적발생솔、위점、류형급기여예후적상관성。결과28례T-ALL환인중，15례（51.57%）환인적NOTCH1기인발생돌변，균위잡합성돌변。돌변환인입원시외주유치림파세포비례급골수유치세포비례여무돌변환인상비균명현승고（P<0.05）。28례환인적일년완해솔위75.0%（21/28），기중돌변환인적일년완해솔위80.0%（12/15），무돌변환인위69.2%（9/13）。차외，3례복발적돌변조환인지일년수방시균이사망（일년시병사솔위20%），이4례복발적무돌변환인경재차화료후지일년수방시균존활（일년시병사솔위0%）。결론인동T-ALL환자중NOTCH1기인돌변발생솔고、위점다양；NOTCH1돌변자초진시질병경엄중，단기예후교호、이복발후만구치료예후경차적추세。
ObjectiveTo clarify the characteristics and clinical signiifcance of the NOTCH1 mutations in childhood T-cell acute lymphoblastic leukemia (T-ALL).MethodsAmplify and sequence the heterodimerization (HD) domain and the pro-line-glutamicacid-serine-threonine (PEST) domain of theNOTCH1 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.ResultsIn 28 children with T-ALL, 15 cases (51.57%) had been identiifed theNOTCH1 mutations, all of which were heterozygous mutations. The lymphoblast counts in peripher-al blood and bone marrow in theNOTCH1 mutant group at admission were signiifcantly higher than in the non-mutant group (P<0.05). 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%).ConclusionsThe children with T-ALL had a high incidence of NOTCH1 mu-tations at various sites. In addition, the patients withNOTCH1 mutations had more severe disease at diagnosis, better short-term prognosis and poor outcome with salvage therapy after relapse.