Application of next generation sequencing technology to the analysis of gene mutations in children with T-acute lymphoblastic leukemia and their impact on prognosis
10.3760/cma.j.cn101070-20240619-00389
- VernacularTitle:基于二代测序技术的儿童急性T淋巴细胞白血病基因突变及其对预后的影响
- Author:
Shuting MAO
1
;
Bai LI
1
;
Dao WANG
1
;
Xinrui WU
1
;
Shufang SU
1
;
Linlin WEI
1
;
Ying LIU
1
;
Fangyuan CHAI
1
;
Yufeng LIU
1
Author Information
1. 郑州大学第一附属医院儿童血液肿瘤科，郑州 450052
- Publication Type:Journal Article
- Keywords:
Gene mutation;
T-acute lymphoblastic leukemia;
Next generation sequencing;
Prognosis
- From:
Chinese Journal of Applied Clinical Pediatrics
2025;40(2):114-119
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To analyze the gene mutation spectrum of children with T-acute lymphoblastic leukemia (T-ALL) using next generation sequencing technology and to evaluate the value of gene mutations in prognosis stratification.Methods:A case series analysis was made.The clinical data of newly diagnosed pediatric T-ALL patients in the First Affiliated Hospital of Zhengzhou University from January 1, 2019 to February 29, 2024 were analyzed retrospectively.T-ALL gene mutations were analyzed.The relationships of gene mutations with clinical features and induction of responses to therapy were studied.The effects of gene mutations on overall survival (OS) and event-free survival (EFS) were examined by the Kaplan-Meier method and COX regression model.Results:A total of 80 newly diagnosed pediatric T-ALL patients were enrolled in the study, with a male-to-female ratio of 3.4∶1.0 and a median age of 8 (range, 2-17) years.A total of 57 mutations were detected in 74 patients, 46.2% (37/74) of whom showed 3 or more gene mutations.The coexistence of mutated genes was obvious. PTEN mutations were more prevalent in male patients ( P=0.018).Initial leukocyte counts were higher in patients with PTEN mutations ( P=0.038) and lower in patients with JAK3 mutations ( P=0.002).Patients with NOTCH1 mutations had a higher positive rate of fusion genes ( P=0.043).Patients with PTEN mutations had a higher rate of minimal residual disease(MRD) remission after 15/19 d of treatment with induction therapy, respectively ( P=0.013).The rate of MRD remission after 33/46 d of treatment with induction therapy was higher in patients with the FBXW7 mutation ( P=0.004) and lower in patients with JAK3 mutations ( P=0.003).Multifactorial COX regression analysis showed that IL7R mutation and three or more gene mutations were independent risk factors for OS and EFS in T-ALL patients(OS: HR=3.252, 7.357, 95% CI: 1.020-10.372, 1.646-32.882; EFS: HR=3.372, 3.009, 95% CI: 1.234-9.214, 1.174-7.708; all P<0.05). Conclusions:Gene mutations are prevalent in T-ALL children and correlate with clinical manifestations and prognosis.The coexistence of mutated genes is obvious.Pediatric T-ALL patients with IL7R mutations and three or more gene mutations have a poorer prognosis.
