DYRK1A and precursor B-cell acute lymphoblastic leukemia: A recent study by Jin et al. (2024) reported that in relapsed/refractory B-ALL models, pharmacologic blockade of DYRK1A–and potentially other CMGC kinases–through EHT1610 and GNF2133 (Liu et al., 2020), led to substantial changes in the alternative splicing of splicing factor transcripts such as RBM39. Specifically, DYRK1A inhibition resulted in the inclusion of a “poison” exon in the nascent RBM39 mRNA, which is recognized by the nonsense-mediated mRNA decay pathway for degradation, resulting in RBM39 protein downregulation and subsequent cell death.