The clinical outcomes and genomic landscapes of acute lymphoblastic leukemia patients with E2A-PBX1: A 10-year retrospective study
The clinical outcomes and genomic landscapes of acute lymphoblastic leukemia patients with E2A-PBX1: A 10-year retrospective study
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E2A-PBX1 急性淋巴细胞白血病患者的临床结果和基因组图谱：一项 10 年回顾性研究
DOI：
10.1002/ajh.26324
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发表时间：
2021
影响因子：
12.8
通讯作者：
Xu Yang
中科院分区：
文献类型：
--
作者：
Zhou Biqi;Chu Xinran;Tian Hong;Liu Tianhui;Liu Hong;Gao Wei;Chen Suning;Hu Shaoyan;Wu Depei;Xu Yang
E2A - PBX1 （TCF3 - PBX1）阳性B细胞急性淋巴细胞白血病（B - ALL）患者的临床结局和基因组特征尚不清楚。回顾性分析了2009年至2019年期间3164例B - ALL患者中137例携带E2A‐PBX1的患者。整个队列的5年总生存率（OS）和无病生存率（DFS）分别为68.6%和61.0%。年龄[DFS，p= 0.037]；累积复发率（CIR），p= 0.005]和诱导化疗后最小残留病水平（MRD） （OS,p= 0.020； DFS,p= 0.002； CIR,p= 0.006）为独立危险因素。在青少年/成人中，异基因造血干细胞移植（allo‐HSCT）在首次完全缓解（CR1）时显著改善了5年预后（OS,p< 0.001； DFS,p< 0.001； CIR,p< 0.001）。与人白细胞抗原匹配的HSCT相比，单倍体HSCT在青少年/成人中降低了CIR （p= 0.017）。在整个队列中，PBX1、PAX5、CTCF和SETD2突变、AKT3扩增和CDKN2A/B缺失是常见的，而在细胞周期、神经生长因子（NGF）信号通路和TP53转录调控方面，青少年/成人与儿童存在转录组差异。诊断时有多个亚克隆的患者往往具有不利的3年预后（DFS,p= 0.010； CIR,p= 0.021）。具有DNA修复基因突变的白血病克隆在这种亚型ALL中表现出侵袭性和治疗难治性表型。我们的研究表明，年龄、MRD水平和DNA修复基因突变与E2A - PBX1阳性B - ALL结果相关。同种异体造血干细胞移植，特别是单倍体造血干细胞移植，可以改善青少年/成人患者的预后。
The clinical outcomes and genomic features of E2A‐PBX1 (TCF3‐PBX1)‐positive B‐cell acute lymphoblastic leukemia (B‐ALL) patients remain unclear. A total of 137 patients carrying E2A‐PBX1 among 3164 B‐ALL patients between 2009 and 2019 were retrospectively analyzed. The 5‐year overall survival (OS) and disease‐free survival (DFS) rates of the whole cohort were 68.6% and 61.0%, respectively. Age [DFS,p= 0.037; cumulative incidence of relapse (CIR),p= 0.005] and the level of minimal residual disease (MRD) after induction chemotherapy (OS,p= 0.020; DFS,p= 0.002; CIR,p= 0.006) were independent risk factors. In adolescents/adults, allogeneic hematopoietic stem cell transplantation (allo‐HSCT) at first complete remission (CR1) significantly improved the 5‐year prognosis (OS,p< 0.001; DFS,p< 0.001; CIR,p< 0.001). Haploidentical HSCT decreased the CIR compared with human leukocyte antigen‐matched HSCT in adolescents/adults (p= 0.017). Mutations in PBX1, PAX5, CTCF and SETD2, amplification of AKT3, and deletion of CDKN2A/B were common in the total cohort, while transcriptome differences were found in the cell cycle, nerve growth factor (NGF) signaling pathway and transcriptional regulation by TP53 between adolescents/adults and children. Patients with multiple subclones at diagnosis tended to have unfavorable 3‐year prognoses (DFS,p= 0.010; CIR,p= 0.021). Leukemia clones with DNA repair gene mutations showed aggressive and treatment‐refractory phenotypes in this subtype of ALL. Our study indicated that age, the level of MRD and DNA repair gene mutations were associated with E2A‐PBX1‐positive B‐ALL outcomes. Allo‐HSCT, especially haploidentical HSCT, could improve the prognosis of adolescent/adult patients.