Adolescents and young adults (AYAs, ~15–39 years) occupy an intermediate position, with declining frequencies of favorable lesions and increasing prevalence of high-risk subtypes, including BCR::ABL1, Ph-like ALL, low hypodiploidy with TP53 mutations, and PAX5 alterations, yet they still retain certain “pediatric-like” molecular features. Here, TP53 is linked to acute lymphoblastic leukemia.