Specifically, B-ALL may feature mutations in histone acetyltransferase CREBBP (18% in relapse ALL, rare in cases without high hyperdiploidy), methyltransferases known as WHSC1 (14–20% in ETV6-RUNX1 and 15% in rearranged TCF3-PBX1), SETD2 (12%, KMT2A(MLL1)- and ETV6-RUNX1 rearranged), EZH2 (1.3%, hypodiploidy), phosphorylases known as JAK2 (10% in high-risk disease, BCR-ABL-like, Down syndrome, high-risk disease), KMT2A(MLL1) (5%), and EP300 (<1%) [33,96,97,98]. This evidence concerns the gene RUNX1 and Down syndrome.