Unexpectedly, the activation of PI3K/AKT was found to be required for ATRA to induce cell differentiation in AML cells, and PI3K/AKT activity elimination counteracted ATRA-induced AML cell differentiation without stimulating cell death, indicating that the simultaneous application of the PI3K/AKT inhibitor limited the maximal therapeutic effect of ATRA. Here, AKT1 is linked to acute myeloid leukemia.