Combined therapy to treat ALL such as BCR-ABL TKIs with a panel of selective PI3K/AKT/mTOR inhibitors in NUP214(CAN)-ABL-positive T-ALL cell lines [78] and the JAK and PI3K inhibitors ruxolitinib and rapamycin in CRLF2-r and JAK-mutated disease [23] are being investigated to maximize the anti-neoplastic effect of different molecular lesions in leukemic cells. This evidence concerns the gene PIK3CD and acute lymphoblastic leukemia.