Targeted amplicon-based next-generation sequencing (54-gene pediatric ALL panel) together with cytogenetic analysis of the bone marrow aspirate identified five independent high-risk genomic lesions: NRAS c.38G > A (p.G13D), JAK2 c.2047C > G (p.R683G), EP300 c.5296C > T (p.Q1766*), P2RY8–CRLF2 fusion, and iAMP21 (Table 2). This evidence concerns the gene EP300 and acute lymphoblastic leukemia.