ATF4 and acute myeloid leukemia: Indeed, MP-A08-induced killing of AML cells occurs via MCL-1 inhibition [18], a mechanism whereby SPHK1 inhibition leads to ceramide accumulation, which was found to directly activate protein kinase R, resulting in the activation of ATF4 and upregulation of NOXA, which in turn leads to the degradation of MCL-1 [16].