IDH1-R123与Notch1突变在儿童急性T淋巴细胞白血病中的作用机制

Mechanism of IDH1-R123 and Notch1 mutations in pediatric acute T lymphocytic leukemia

目的探讨IDH1-R123与Notch1双突变对儿童急性T淋巴细胞白血病(ALL)的作用及机制。方法选择2016年5月~2017年12月丽水市人民医院儿童ALL患者58例作为对象,所有患者入院后均完成IDH1-R123与Notch1双突变基因测序,确定IDH1-R123与Notch1双突变在儿童急性T淋巴细胞白血病中的突变率及突变特征,入组患者均给予诱导、巩固及维持治疗,两组治疗后均完成24个月随访,比较突变儿童与非突变儿童生化指标、临床特征及预后。结果58例儿童ALL患者中33例IDH1-R123与Notch1双突变,突变率为56.90%;突变儿童血WBC计数、平均血红蛋白高于非突变儿童(P<0.05);突变儿童平均血小板数低于非突变儿童(P<0.05);ALL IDH1-R123突变25例,占43.10%,突变位于WD40区域,且均为点突变;Notch1突变8例,占13.79%,突变位点主要位于HD区域和PEST结构域。其中,HD突变5例,占62.50%,均为氨基酸位点为233;PEST结构域3例,占37.50%;突变儿童与非突变儿童6个月、12个月生存率无统计学意义(P>0.05);突变儿童18个月、24个月生存率低于非突变儿童(P<0.05)。结论IDH1-R123与Notch1双突变在儿童急性T淋巴细胞白血病中突变率较高,且与患者不良预后有关,有助于指导临床诊疗。

Objective To investigate the effect and mechanism of IDH1-R123 and Notch1 double mutations on pediatric acute T lymphocytic leukemia(ALL).Methods From May 2016 to December 2017,58 children with ALL in Lishui People's Hospital were selected as subjects.All patients completed IDH1-R123 and Notch1 double mutation genes sequencing after admission,so as to determine the mutation rate and mutation characteristics of IDH1-R123 and Notch1 double mutations in pediatric acute T lymphocytic leukemia.All patients were given induction,consolidation and maintenance for treatments.The two groups were followed up for 24 months after treatment.The biochemical indicators,clinical characteristics,and prognosis of children with mutation and non-mutation were compared.Results Among the 58 children with ALL,there were 33 cases with IDH1-R123 and Notch1 double mutations,and the mutation rate was 56.90%.The blood WBC count and average hemoglobin in the children with mutation were higher than those of children without mutation(P<0.05).The average platelet count of children with mutation was lower than that of children without mutation(P<0.05).There were 25 cases of ALL IDH1-R123 mutations,accounting for 43.10%.The mutations were located in the WD40 region and were all point mutations.There were 8 cases of notch1 mutation,accounting for 13.79%.The mutation sites were mainly located in the HD region and the PEST domain.Among them,there were 5 cases of HD mutations,accounting for 62.50%,which were all at the amino acid site of 233;there were 3 cases in PEST domain,accounting for 37.50%.The differences in the 6-month and 12-month survival rates of children with mutation and without mutation were not statistically significant(P>0.05).The survival rate of children with mutation at 18 and 24 months was lower than that of children without mutation(P<0.05).Conclusion IDH1-R123 and Notch1 double mutations have a higher mutation rate in children with acute T lymphocytic leukemia,and are associated with poor prognosis of patients,which can help guide clinical diagnosis and treatment.