To identify which of the 22 NUDIX hydrolases regulate the cytotoxic effects of thiopurines, we performed a NUDIX-targeted CRISPR/Cas9 screen in 2 human B-ALL cell lines, Nalm6 (DUX4-IGH rearranged B-ALL) and 697 (TCF3-PBX1 fusion B-ALL) (Figure 1A). Here, DUX4 is linked to acute lymphoblastic leukemia.