Liu Qinglin, Yu Xiang, Wen Jinquan, Yin Nange, Liao Xin, Zou Pinli, Guo Yuxia, Song Lin, Xiao Jianwen
First Clinical College of Chongqing Medical University, Chongqing, China.
Ministry of Education Key Laboratory of Child Development and Disorders, Chongqing, China.
Front Pediatr. 2023 Aug 16;11:1224966. doi: 10.3389/fped.2023.1224966. eCollection 2023.
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).
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.
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 ( < 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, ( > 0.05); however, the mean survival time of the IR group was longer than that of the HR group ( < 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.
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.
探讨晚期T细胞淋巴母细胞淋巴瘤（T-LBL）的基因组特征和预后，并研究T-LBL与T细胞急性淋巴细胞白血病（T-ALL）之间的关系。
招募35例患有Ⅲ期或Ⅳ期疾病的中国T-LBL儿童进行本研究。他们接受了联合化疗和全外显子测序。研究临床特征、预后与特定基因突变之间的关系。从数据库下载T-LBL和T-ALL的基因芯片，并分析差异基因表达。
2例患者检测到种系致病基因突变（CARS或MAP2K2）；35例患者共鉴定出3.06±2.21个体细胞致病基因突变，且在NOTCH1、FBXW7、PHF6和JAK3基因中观察到体细胞突变。NOTCH1突变与FBXW7突变显著相关，NOTCH1-FBXW7突变患者的诊断年龄小于无此类突变的患者（<0.05）。32例患者达到完全缓解（CR），14例和18例患者分别被分为中危（IR）组和高危（HR）组。在中位随访44个月期间，3例患者复发。三年无事件生存率（pEFS）为82.286%，不同性别、年龄或NOTCH1-FBXW7突变状态的pEFS无显著差异（>0.05）；然而，IR组的平均生存时间长于HR组（<0.05）。使用R包limma分析T-LBL和/或T-ALL数据集中基因的差异表达，发现1/3的差异表达基因在T-ALL和T-LBL数据集中均有出现。在T-LBL数据集中发现PI3K-Akt信号通路基因和USP34基因高表达。
尽管T-ALL和T-LBL均起源于前体T细胞，被认为是同一种疾病的不同表现形式，且采用基于T-ALL的化疗时T-LBL的预后良好，但T-LBL和T-ALL之间的基因分布存在差异。PI3K-Akt信号通路和USP34基因似乎在T-LBL中发挥重要作用，但靶向USP34基因或PI3K-Akt通路的药物可能无效。
