Ikeda et al. [64] also demonstrated that CDDO-Im selectively downregulated expression of PML-RARα fusion protein with an activation of caspase 8, which might contribute to enhanced ATRA-induced differentiation in APL cells, and arsenic-trioxide- (ATO-) induced apoptosis in both ATRA-sensitive NB4 and resistant R2 cell lines and primary APL cells. Here, CASP8 is linked to acute promyelocytic leukemia.