Model for EZH2 functional switch from a polycomb repressor to a transcriptional activator in NK lymphoma. JAK3 overactivation leads to phosphorylation of EZH2 at Y244. This phosphorylation event shifts EZH2 from a transcriptional repressor associated with PRC2 to a transcriptional coactivator cooperating with Pol II. This study suggests that blocking EZH2 phosphorylation by JAK3 inhibitor (JAK3i) is a potential therapeutic strategy to inhibit EZH2 noncanonical oncogenic function in NKTL. PcG, polycomb group.