Clinical relevance of etoposide CRISPR screen and etoposide pharmacology genes. (A) Schematic showing anticipated relationship between significant hits from CRISPR screen and association with clinical outcome in AML. (B) Flowchart and summary results of association analysis between diagnostic leukemic cell gene expression levels of EtoRGs (n = 10 genes) and EtoSGs (n = 40 genes) with 4 clinical outcome endpoints (EFS, OS, RR, and MRD1) in pediatric patients with AML from St Jude AML02 trial. Twenty-six genes significantly associated with at least 1 clinical outcome (P < .05 in Cox proportional hazard, fine method of Gray, and logistic regression) are listed; of these, 19 showed significant association with consistent direction. (C) Etoposide pharmacology pathway (PharmGKB.org) highlighting roles of ABCC1 and TOP2A. (D) Kaplan-Meier survival curves showing high ABCC1 expression and low TOP2A expression associated with poor OS and EFS (∗, ∗∗, ∗∗∗ indicate significant terms at the P < .05, P < .01, and P < .001 statistical levels, respectively). Gene expression association analysis was performed with (referred as Risk adj) or without adjusting (referred as Unadj) for initial risk–group assignment.