Loss-of-Function Mutations of BCOR Are an Independent Marker of Adverse Outcomes in Intensively Treated Patients with Acute Myeloid Leukemia

Acute myeloid leukemia (AML) is characterized by recurrent genetic events. The corepressor and its homolog, the , have been reported to be rare but recurrent mutations in AML. Previously, smaller studies have reported conflicting results regarding impacts on outcomes. Here, we retrospectively analyzed a large cohort of 1529 patients with newly diagnosed and intensively treated AML. and mutations were found in 71 (4.6%) and 53 patients (3.5%), respectively. Frequently co-mutated genes were , and . Mutated and loss-of-function mutations of were significantly more common in the ELN2017 intermediate-risk group. Patients harboring loss-of-function mutations of had a significantly reduced median event-free survival (HR = 1.464 (95%-Confidence Interval (CI): 1.005-2.134), = 0.047), relapse-free survival (HR = 1.904 (95%-CI: 1.163-3.117), = 0.01), and trend for reduced overall survival (HR = 1.495 (95%-CI: 0.990-2.258), = 0.056) in multivariable analysis. Our study establishes a novel role for loss-of-function mutations of regarding risk stratification in AML, which may influence treatment allocation.