AML-1196: The molecular and clinicopathological landscape of core-binding factor acute myeloid leukemia: a retrospective study

Abstract

Context: Acute myeloid leukemia (AML) with core-binding factor (CBF) rearrangements, encompassing t(8;21)(q22;q22) and inv(16)(p13.1q22)/t(16;16)(p13.1;q22), represents a distinct biological and clinical subset of AML. Objective: Comprehensively characterize the molecular and clinicopathological features of CBFAML through retrospective analysis, with the aim of identifying prognostic markers. Design/Methods: We retrospectively analyzed diagnosed cases of CBF-AML. Clinical features, hematological parameters, immunophenotypic profiles, cytogenetic and molecular findings, minimal residual disease (MRD) status, and survival outcomes were analyzed. Survival outcomes were analyzed using Kaplan–Meier survival analysis. Results: Among 192 CBF-AML patients (pediatric: 112; adult: 80), 165 had AML1-ETO/t(8;21), and 29 had CBFB-MYH11/inv(16). The median age was 14.5 (range 1–59) years, with a male:female ratio of 2.4:1. At presentation, the median hemoglobin was 7.3 g/dL, white blood cell count 17 × 10⁹/L, platelets 28 × 10⁹/L, and LDH 638 IU/L. Median peripheral blood and bone marrow blast percentages were 55% and 65%, respectively. Immunophenotypic analysis showed frequent co-expression of CD34, CD13, CD33, and HLA-DR across CBF-AML cases. Aberrant expression of CD56 (76% vs 28%) and CD19 (57.6% vs 7.7%) was more prevalent in cases with AML1-ETO, whereas aberrant expression of CD36 (28% vs 12.2%) and CD14 (20.8% vs 8%) was more common in cases with CBFB-MYH11. FLT3 mutation was observed in 9.1% of cases; NPM1 mutation was very rare, in 0.5% of cases. Additional cytogenetic abnormalities and complex karyotypes were detected in 52.6% and 10.3% of all cases, respectively, and were more prevalent in cases with AML1-ETO than in cases with CBF-MYH11. All patients received intensive induction chemotherapy, primarily the “7+3” regimen. Complete remission after induction was achieved in 77.8% of cases, and MRD negativity was observed in 64.3% of evaluable patients and was associated with significantly improved relapse-free survival (P < 0.001) and overall survival (P < 0.001). Patients with CBFB-MYH11 (inv(16)) demonstrated higher rates of complete remission and MRD negativity than those with AML1-ETO (t(8;21)). Conclusions: This study highlights the molecular and immunophenotypic differences between CBF-AML subtypes, with AML1-ETO linked to CD56/CD19 expression and complex karyotypes, and CBFB-MYH11 associated with CD14/CD36 expression and better responses. MRD negativity post induction strongly predicted improved survival.