Here we demonstrate that downregulation of FBXL10 results in a decrease of PcG binding and the associated H2AK119ub1 and H3K27me3 levels at the DUSP6 promoter, thus confirming DUSP6 as a direct target of FBXL10 in DLBCL cells. Here, DUSP6 is linked to diffuse large B-cell lymphoma.