Genomic signatures and prognosis of advanced stage Chinese pediatric T cell lymphoblastic lymphoma by whole exome sequencing

作者全名："Liu, Qinglin; Yu, Xiang; Wen, Jinquan; Yin, Nange; Liao, Xin; Zou, Pinli; Guo, Yuxia; Song, Lin; Xiao, Jianwen"

作者地址："[Liu, Qinglin] Chongqing Med Univ, Clin Coll 1, Chongqing, Peoples R China; [Yu, Xiang; Yin, Nange; Liao, Xin; Zou, Pinli; Guo, Yuxia; Song, Lin] Minist Educ, Key Lab Child Dev & Disorders, Chongqing, Peoples R China; [Yu, Xiang; Yin, Nange; Guo, Yuxia] Natl Clin Res Ctr Child Hlth & Disorders, Chongqing, Peoples R China; [Yu, Xiang; Xiao, Jianwen] Chongqing Key Lab Pediat, Chongqing, Peoples R China; [Wen, Jinquan] Hosp Xianyang Caihong, Dept Pediat Hematol, Xianyang, Shaanxi, Peoples R China; [Yin, Nange; Song, Lin] Chongqing Med Univ, Dept Pharm, Childrens Hosp, Chongqing, Peoples R China; [Liao, Xin; Zou, Pinli; Guo, Yuxia; Xiao, Jianwen] Chongqing Med Univ, Dept Hematol, Childrens Hosp, Chongqing, Peoples R China; [Xiao, Jianwen] China Int Sci & Technol Cooperat Base Child Dev &, Chongqing, Peoples R China"

通信作者："Xiao, JW (通讯作者)，Chongqing Key Lab Pediat, Chongqing, Peoples R China.; Xiao, JW (通讯作者)，Chongqing Med Univ, Dept Hematol, Childrens Hosp, Chongqing, Peoples R China.; Xiao, JW (通讯作者)，China Int Sci & Technol Cooperat Base Child Dev &, Chongqing, Peoples R China."

来源：FRONTIERS IN PEDIATRICS

ESI学科分类：CLINICAL MEDICINE

WOS号：WOS:001058679300001

JCR分区：Q2

影响因子：2.1

年份：2023

卷号：11

期号：　

开始页：　

结束页：　

文献类型：Article

关键词：T cell lymphoblastic lymphoma; children; whole exome sequencing; PI3K-Akt pathway; USP34 gene

摘要："Objective To investigate the genomic signatures and prognosis of advanced-stage T cell lymphoblastic lymphoma (T-LBL) and to examine the relationship between T-LBL and T cell acute lymphoblastic leukemia (T-ALL). Methods 35 Chinese T-LBL children with stage III or IV disease were recruited for this study. They were treated with combination chemotherapy and whole exome sequencing. The relationship of the clinical features, prognosis and specific gene mutations was researched. Gene chips of T-LBL and T-ALL were downloaded from a database, and differential gene expression was analyzed. Results Germline causal gene mutations (CARS or MAP2K2) were detected in 2 patients; 3.06 +/- 2.21 somatic causal gene mutations were identified in the 35 patients, and somatic mutations were observed in the NOTCH1, FBXW7, PHF6 and JAK3 genes. NOTCH1 mutations were significantly associated with FBXW7 mutations, and the age at diagnosis of patients with NOTCH1-FBXW7 mutations was less than that of patients without such mutations (P < 0.05). 32 patients achieved complete remission (CR), and 14 and 18 patients were classified into the intermediate risk (IR) group and high risk (HR) group. During a median follow-up of 44 months, 3 patients relapsed. Three-year prospective event free survival (pEFS) was 82.286%, and no significant differences of pEFS were found for different sexes, ages, or statuses of NOTCH1-FBXW7 mutations, (P > 0.05); however, the mean survival time of the IR group was longer than that of the HR group (P < 0.05). Differential expression of genes in the T-LBL and/or T-ALL datasets was analyzed using the R package limma, and 1/3 of the differentially expressed genes were found in both the T-ALL and T-LBL datasets. High expression of PI3K-Akt signal pathway genes and the USP34 gene was found in the T-LBL dataset. Conclusion Although T-ALL and T-LBL both originate from precursor T-cells and are considered different manifestations of the same disease and the outcome of T-LBL is favorable when using T-ALL-based chemotherapy, there are differences in the gene distribution between T-LBL and T-ALL. It seems that the PI3K-Akt signaling pathway and the USP34 gene play important roles in T-LBL, but medicines targeting the USP34 gene or the PI3K-Akt pathway may be invalid."

基金机构：The study was supported by the National Natural Science Foundation of China (Project No. 81900162) and the Chongqing Science and Technology Commission of the PR China (Project No. cstc2018jsyj-jsyjX0015); the funding sources had no roles in the design and [cstc2018jsyj-jsyjX0015]; National Natural Science Foundation of China; Chongqing Science and Technology Commission of the PR China; [81900162]

基金资助正文："We thank the patients and their families who participated in this study. The authors declare that there are no competing interests associated with the manuscript.r The study was supported by the National Natural Science Foundation of China (Project No. 81900162) and the Chongqing Science and Technology Commission of the PR China (Project No. cstc2018jsyj-jsyjX0015); the funding sources had no roles in the design and conduct of the study collection; management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and the decision to submit the manuscript for publication. The study was registered at the Chinese Clinical Trail Registry and the clinical study registration (ChiCTR1900025690 and ChiCTR-IPR-14005706)."