Model based on molecular mutations. (A) Categorization of all mutations detected in AML to 5 prognostic groups. The cohort was stratified according to an “entity-based” hierarchy: (1) PML-RARA, CEBPA double-mutated (n = 71); (2) RUNX1-RUNX1T1, CBFB-MYH11, NPM1mut/FLT3-ITD⁻ (n = 252); (3) CEBPA single-mutated, NPM1mut/FLT3-ITD⁺, FLT3-ITD⁺, wild-type cases (n = 235); (4) MLL-PTD and/or RUNX1mut and/or ASXL1mut (n = 203); (5) TP53 mutations (n = 80). (B-C) Kaplan-Meier plots for the molecular mutation-based model, which separates patients into 5 prognostic subgroups: (1) PML-RARA, CEBPA double-mutated (n = 71); (2) RUNX1-RUNX1T1, CBFB-MYH11, NPM1mut/FLT3-ITD⁻ (n = 252); (3) CEBPA single-mutated NPM1mut/FLT3-ITD⁺, FLT3-ITD⁺, wild-type cases (n = 235); (4) MLL-PTD and/or RUNX1 and/or ASXL1 (n = 203); (5) TP53 mutations (n = 80). (B) OS (P values between the subgroups are 1 vs 2, P = .004; 2 vs 3, P = .001; 3 vs 4, P = .001; 4 vs 5, P < .001, respectively). (C) EFS (P values between the subgroups are 1 vs 2, P = .001; 2 vs 3, P = .011; 3 vs 4, P = .004; 4 vs 5, P < .001, respectively). (D-E) Comparison of cytogentic and molecular genetic model. Cohort subdivided according to (D) cytogenetics and (E) molecular mutations. The model based on molecular mutations leads to 5 prognostic subsets instead of 3 in the cytogenetic model and thus a refined assignment of patients to distinct prognostic groups with large differences in outcome.