Ex vivo drug vulnerabilities. (A) Activity of compounds in human cell lines of AEL and NUP98-KDM5A rearranged AML and in primary cells from the established mouse models of AEL, AML, and B/T-ALL. The heatmap indicates area under the curve (AUC) values for each compound per leukemia sample; red indicates higher sensitivity. The 2 positive controls used in the drug screening (bortezomib [BORT] and panobinostat [PANO]) are in bold. Distribution of AUC values (y-axis) for each compound (x-axis) in CHFR-2811 human cells expressing NUP98-KDM5A and mouse primary NUP98-KDM5A–expressing AML cells (B), AEL leukemia mouse models (#1651 and #1483) with mutations in Trp53, Bcor, and Dnmt3a (C), and AEL leukemia mouse models (#4497 and #4499) with mutations in Trp53 and Bcor but wild-type Dnmt3a (D). The topmost effective drugs (higher AUC values) are highlighted by colored dots in each panel. The 2 positive controls (BORT and PANO) are highlighted in gray.