Co-mutation of BCOR and BCORL1 was associated with favorable outcome in the adverse risk patients with Acute Myeloid Leukemia

Abstract

Abstract Introduction Mutations in BCOR (BCL6 corepressor) and its homolog BCORL1 (BCL6 corepressor-like 1) are closely associated with the pathogenesis and progression of acute myeloid leukemia (AML). BCOR mutation (BCORmut) is an adverse marker for AML in 2022 ELN risk stratification. Several studies reported that AML patients with BCORL1 mutation (BCORL1mut) was associated with poor outcomes. However, there are rare data on AML with co-mutation of BCOR and BCORL1 (BCORmut/BCORL1mut). Therefore, we integrated clinical and genomic features to assess its impact on outcomes in patients with AML.Methods Consecutive newly diagnosed AML patients from January 2017 to May 2025 at Peking University People's Hospital were included. were included. Clinical and genetic data were collected and analyzed. Cox regression model was used to identify the variables associated with relapse-free survival (RFS) and survival.ResultsIn newly diagnosed 2209 AML patients, BCORmut/BCORL1mut was detected in 38 (2%) patients; BCORmutor BCORL1mut was detected in 72 (3%) or 31 (1%) patients, respectively. Since the majority of the patients (n = 115, 82%) with BCORmutand/or BCORL1mut were classified in the ELN adverse risk group, we focused on the adverse risk group. Among the 782 patients with adverse risk, 439 (56%) were male. Median age was 52 years (IQR, 38–62 years). With a median follow-up of 16 months (IQR, 8-32 months) for all patients and 22 months (IQR, 12-38 months) for survivors, 393 (50%) patients received intensive chemotherapy; 389 (50%), less intensive chemotherapy. 577 (74%) patients ultimately achieved CR /CRi. 359 (46%) patients underwent transplant. The 3-year probabilities of RFS and survival were 53% (95% confidence interval [CI], 48, 58%) and 52% (49, 59%). The 782 patients were divided into 4 subgroups: BCORmut/BCORL1mut (n = 37, 5%), BCORmut/BCORL1wt (n = 65, 8%), BCORwt/BCORL1mut (n = 13, 2%) and BCORwt/BCORL1wt (n = 667, 85%). Monomeric karyotype (p = 0.003), complex karyotype (p = 0.001), t(v;11q23.3) (p = 0.001), Chr7 abnormalities (p = 0.030), Chr17 abnormalities and/or TP53 mutation (p < 0.001) were the least common and the final CR/CRi rate was the highest (p = 0.015) in the BCORmut/BCORL1mut subgroup compared to others. The 3-year probabilities of RFS (82% vs. 62% vs. 50% vs. 51%, p = 0.021) and survival (93% vs. 71% vs. 58% vs. 50%, p = 0.001) in the BCORmut/BCORL1mut subgroup were the highest compared with BCORmut/BCORL1wt, BCORwt/BCORL1mut and BCORwt/BCORL1wt subgroups. In multivariate analyses BCORmut/BCORL1mut was significantly-associated with favorable RFS (HR = 0.3 [0.1, 0.6], p = 0.003) and survival (HR = 0.2 [0.1, 0.6], p = 0.004). In addition, increasing WBC count at diagnosis, secondary AML, MRD positivity after achieving CR, nontransplant, complex karyotype, t(v; 11q23), t(9; 11), increasing the number of mutations, NPM1wt/FLT3-ITDwt, NPM1wt/FLT3-ITDmut, CBL mutation, ASXL1 mutation, GATA2 mutation, NRAS mutation, TET2 mutation, Chr17 abnormalities and/or TP53 mutation, poor RFS and/or survival.ConclusionsOur study suggested that co-mutation in BCOR and BCORL1 was associated with favorable outcomes in the adverse risk patients with AML. Our conclusion needs to be confirmed by a large cohort prospective study.