[Prognostic impact of WT1 mutations in patients with acute myeloid leukemia].

Objective: To investigate the prognostic impact of WT1 mutations in patients with acute myeloid leukemia (AML) . Methods: This was a retrospective cohort study. A total of 1 583 patients with AML who were admitted to the Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, from January 2015 to March 2024 were enrolled in the study, including 1 437 WT1 wild-type patients and 146 (9.2%) carrying WT1 mutations. Clinical characteristics and gene mutation profiles were comprehensively compared between WT1-mutated and wild-type cohorts. Survival analyses were performed on WT1-mutant and WT1 wild-type patients in accordance with the 2022 ELN risk classification and major AML mutation subgroups. The primary outcome measures included overall survival (OS), relapse-free survival (RFS), and event-free survival (EFS) . Results: No statistically significant difference in clinical characteristics was found between WT1-mutant and WT1 wild-type patients (all P>0.05). In addition, WT1-mutant AML displayed a unique genomic alteration profile, which is characterized by high frequencies of CEBPA(bZIP) (30.1% vs 15.0%, P<0.001) and FLT3-ITD (30.1% vs 19.8%, P=0.036), along with a reduced incidence of NPM1 (11.0% vs 20.4%, P=0.068) and RUNX1::RUNX1T1 (4.8% vs 19.2%, P<0.001). Survival analysis of the entire cohort and within the 2022 ELN risk classification revealed no significant differences in OS, RFS, or EFS between WT1-mutated and wild-type groups (all P>0.05). Although WT1 mutations had no significant prognostic impact on different AML subgroups, WT1 mutations were associated with inferior RFS (P=0.042) and EFS (P=0.017) in patients co-mutated with CEBPA(bZIP). Clinical factors, including age, sex, and common AML mutation genes, were incorporated into multivariate Cox regression analyses, which consistently showed that WT1 was not an independent prognostic risk factor (OS: P=0.209, HR=0.796, 95%CI: 0.558-1.137; RFS: P=0.390, HR=1.149, 95%CI: 0.837-1.579; EFS: P=0.180, HR=1.192, 95%CI: 0.922-1.542) . Conclusion: Although WT1 is a common mutation gene in AML, it was not associated with poor prognosis and was not an independent prognostic risk factor in our cohort.