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.

中文翻译：

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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


E2A-PBX1 (TCF3-PBX1) 阳性 B 细胞急性淋巴细胞白血病 (B-ALL) 患者的临床结果和基因组特征仍不清楚。回顾性分析2009年至2019年间3164例B-ALL患者中总共137例携带E2A-PBX1的患者。全队列的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]和诱导化疗后微小残留病（MRD）水平（OS， p = 0.020；DFS， p = 0.002；CIR， p = 0.006）是独立危险因素。在青少年/成人中，首次完全缓解 (CR1) 时的同种异体造血干细胞移植 (allo-HSCT) 显着改善了 5 年预后（OS， p < 0.001；DFS， p < 0.001；CIR， p < 0.001）。与青少年/成人中人类白细胞抗原匹配的 HSCT 相比，单倍体 HSCT 降低了 CIR ( p = 0.017)。 PBX1、PAX5、CTCF 和 SETD2 突变、AKT3 扩增和 CDKN2A/B 缺失在整个队列中很常见，而细胞周期、神经生长因子 (NGF) 信号通路和 TP53 转录调控方面存在转录组差异青少年/成人和儿童之间。诊断时具有多个亚克隆的患者往往有不利的 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 ALL 亚型中表现出侵袭性和难治性表型。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 结局相关。 Allo-HSCT，特别是半相合HSCT，可以改善青少年/成年患者的预后。