Other lesions identified by NGS in B-lineage ALL, are represented by mutations in CREBBP and its paralogue, EP300 (p300),72 which were identified in the relapse samples and appear to be more frequent in hyperdiploid relapsed cases.73 Similarly, NT5C2 mutations, which confer increased enzymatic activity on the NT5C2 protein, which normally dephosphorylates nucleoside analogs, such as mercaptopurine, used in consolidation and maintenance therapy, have been described. Here, NT5C2 is linked to acute lymphoblastic leukemia.