Figure 5.

Oncogenic driver events, transcriptional identity, and leukemia stemness all contribute to outcome in pediatric myeloid-related acute leukemias. A, Integrative Cox proportional hazards model to look at associations with overall survival in the discovery cohort (38). Each bar represents the −log₁₀ P value of covariates and their association with survival. The covariates used in the model to calculate the P value are indicated below the graph with a check mark. Immunophenotype as a single covariate failed to reach statistical significance. B, Probability of EFS (pEFS) of an ongoing multi-institutional prospective pediatric AML trial (AML16) and the proposed classification scheme based on this article for the validation cohort. See Supplementary Figs. S22 and S23 for results of each independent cohort. C, Performance of the proposed genomic classification relative to that utilized in an ongoing prospective upfront pediatric AML study (NCT03164057) in terms of discrimination capability (left) and percentage of high-risk or low-risk classified patients (right) culminating in a risk classification utility score (top, right) for the validation cohort. See Supplementary Figs. S24 and S25 for results of each independent cohort. D, Working model. Mutational events in distinct hematopoietic progenitor subsets lead to transformation, and both components contribute to the transcriptional identity and leukemia stemness. Chemotherapy sensitivity and therefore outcomes are a composite of these factors.