In particular, all the B-ALL cases harbored single gene variants involving CREBBP, FLT3, JAK2, PAX5, and TP53. On the contrary, in all the T-ALL-derived samples, we observed the presence of at least two gene variants, with a statistically significant increase of the mutations number in T-lineage patients compared to B-ALL cases. This evidence concerns the gene CREBBP and acute lymphoblastic leukemia.