Asciminib is a novel inhibitor of ABL1 and ABL2 gene fusions in ALL but requires the ABL SH3 domain for efficacy

High-risk Ph-like ALL includes genomic rearrangement of the ABL1 and ABL2 genes (collectively ABL-rearranged, ABLr), and novel treatments are required. For the first time, we demonstrate asciminib efficacy in ABLr ALL, but only when the ABL SH3 domain is present.