Synergistic Targeting of Menin in AML
Menin inhibitors have demonstrated profound preclinical activity in MLL1-rearranged and NPM1 mutated AML and in this context, ziftomenib is a novel compound currently assessed in a clinical phase I/II trials. We assessed preclinical effects of ziftomenib and demonstrate profound synergy in combination with compounds targeting chromatin regulation and apoptosis including the BCL2 inhibitor venetoclax which was validated in primary AML samples and an MLL-r and NPM1 mutated AML xenograft model. Overall design: RNA sequencing of indicated cell lines treated with 150nM ziftomenib (KO-539) or DMSO for 4 days in OCI-AML3 and MOLM13  and 3 days in MV411. OCI-AML3 were additionally treated with 100nM VTP-50469 or DMSO for 4 days. All experiments performed in triplicates.