MYC and acute lymphoblastic leukemia: Prominent was control of ribosome biogenesis, including expression of RNA polymerase I (POL I) subunits, the importance of which was validated by inhibition of <i>BCR::ABL1</i> cells by POL I inhibitors, including CX-5461, that prevents promoter recruitment and transcription initiation by POL I. Our results reveal an essential ERG- and c-MYC-dependent transcriptional network involved in regulation of metabolic and ribosome biogenesis pathways in <i>BCR::ABL1</i> B-ALL, from which previously unidentified vulnerabilities and therapeutic targets may emerge.