Conversely, knockout of TSC1, an upstream negative regulator of mTORC1 signaling, partially rescued the decreased viability of KARPAS422 cells following VTP50469 treatment (Supplementary Fig. 8f), supporting a functional role of mTORC1 signaling in EZH2 mutant DLBCL cells’ hypersensitivity to MEN1 inhibition. Here, TSC1 is linked to diffuse large B-cell lymphoma.