AFF1 and acute lymphoblastic leukemia: We performed a domain-specific kinome-wide CRISPR screen in genetically diverse high-risk ALL cell lines SEM (KMT2A::AFF1) and HAL-01 (TCF3::HLF) and TVA-1 (ETV6::ABL1) cells previously immortalized from a Ph-like ALL patient-derived xenograft (PDX) model [30] to identify novel druggable targets in high-risk ALL (Fig. 1A).