Finally, we established a PDX from a diagnostic sample obtained from a child with High Hyperdiploid B-ALL, harboring a heterozygous deleterious insertion mutation in CREBBP, alongside an NRASG12C activating mutation, and who responded poorly to treatment, as evidenced by the presence of high-risk measurable residual disease (2.3%) at the end of induction. The gene discussed is CREBBP; the disease is acute lymphoblastic leukemia.