Our findings provide new insight into the mechanism of wogonoside-induced differentiation and anti-leukemic effect of primary AML cells in association with activation of PLSCR1 nuclear function, which highlights a role of the PLSCR1-IP3R1-Ca2+ cascade, implicating the therapeutic potential of wogonoside for AML malignancies, especially for non-APL AML. This evidence concerns the gene PLSCR1 and acute promyelocytic leukemia.