A 3-gene PI stratifies survival in AML patients (discovery and validation series). (A) Forest plot displaying hazard ratios and 95% CIs from univariate and multivariate analyses of PI, standard prognosticators, and molecular lesions predictive of survival (discovery series). (B-F) A 3-gene PI stratifies survival in adult nonpromyelocytic AML patients (German, TCGA, and Beat AML validation series; N = 905 in total) and in childhood AML (TARGET series; n = 145). We used X-tile for the identification of the optimal PI cut-point parsing the patient populations into subgroups with statistically significant differences in survival probabilities across gene-expression platforms (https://medicine.yale.edu/lab/rimm/research/software.aspx). For the German and TARGET series, PI scores <1.0 were defined as low, PI scores between 1.0 and 1.5 were defined as intermediate, and PI scores >1.5 were defined as high. For the TCGA and Best AML series, PI scores <1.4 were defined as low, PI scores between 1.4 and 2.0 were defined as intermediate, and PI scores >2.0 were defined as high. Kaplan-Meier estimates of OS in adults and children with AML from 5 independent validation series. Patients were stratified by low, intermediate, or high PI (German series, TCGA, and Beat AML series) or by median PI values (TARGET AML series). We used X-tile, a bioinformatics tool for outcome-based cut-point optimization, for the identification of the optimal PI values parsing the patient populations into subgroups with statistically significant differences in survival probabilities.24 Survival curves were compared using a log-rank (Mantel-Cox) test. (B) Kaplan-Meier estimates of OS in 535 adult patients (German series). (C) Kaplan-Meier estimates of OS in a subgroup of 223 adult patients with CN AML (German series). (D) Kaplan-Meier estimates of OS in 128 adult patients with nonpromyelocytic AML (TCGA series). (E) Kaplan-Meier estimates of OS in 242 adult patients with nonpromyelocytic AML (Beat AML series). (F) Kaplan-Meier estimates of OS in 96 children with non-CBF AML from TARGET.