EIF2AK4 and acute myeloid leukemia: In contrast, in both AML and mantle cell lymphoma (MCL) cell lines, ONC201 was shown to stimulate phosphorylation of GCN2 and eIF2α; however, eIF2α was found to be dispensable for ATF4 induction, suggesting that ONC201 stimulates a non-canonical ISR in hematologic malignancies [74].