PI3K–AKT–MTOR pathway activated by BCR–ABL1. Rapamycin (sirolimus) and dual PI3K/MTOR inhibitor effective in vitro on Ph+ ALL patient samples and synergy with TKI (54, 171). MTOR has also been implicated in mediating steroid resistance (56). Multiple agents in clinical trials in relapsed/refractory ALL, including TORC1/2 inhibitors (AP23573) for relapsed leukemia. This evidence concerns the gene ABL1 and leukemia.