JOURNAL ARTICLE
RESEARCH SUPPORT, NON-U.S. GOV'T
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The clinical outcomes and genomic landscapes of acute lymphoblastic leukemia patients with E2A-PBX1: A 10-year retrospective study.

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.

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