The inclusion of targeted panel sequencing in protocols, such as those of the PETHEMA group, and, in particular, the assessment of TP53 status in B-ALL, and NOTCH1, KRAS, NRAS, and FBXW7 in T-ALL (NCT04179929), has made it possible to evaluate mutational profiles and make decisions for the benefit of patients. This evidence concerns the gene NOTCH1 and acute lymphoblastic leukemia.