Menin inhibition impairs metastatic colonization of Ewing sarcoma

In MLL-rearranged leukemias, Menin:MLL interactions drive leukemogenesis and Menin inhibitors have been FDA approved for these cancers. We previously reported that Menin promotes oncogenic phenotypes in Ewing sarcoma (EwS).

Here, we sought to define EwS-specific functions of Menin and determine if Menin inhibitors could be therapeutically leveraged for these tumors. Genetic knockout of Menin had no impact on EwS cell proliferation in vitro, but metastatic potential of Menin-depleted cells in vivo was impaired. Transcriptional profiling of Menin knockout cells in vitro showed reproducible downregulation of MYC signature genes and upregulation of developmental programs.