Low-hypodiploid ALL is characterized by TP53 mutations in the leukemia cells in more than 90% of cases and also in the germline in approximately 50% of patients, in addition to the somatic alterations in IKZF2 and RB1. Therefore, patients with low-hypodiploid ALL should undergo germline testing for TP53 germline pathogenic variants (i.e., Li–Fraumeni syndrome) to enable treatment modification to avoid the use of carcinogenic agents and for genetic consultation purposes [36]. This evidence concerns the gene TP53 and acute lymphoblastic leukemia.