Potential targets of EZH2 in extranodal NKTL. (A) The majority of the currently investigated EZH2 small-molecule inhibitors hamper methylation of H3K27, resulting in decreased transcription repression. However, this strategy may not prove beneficial in extranodal NKTL. (B) MELK-mediated phosphorylation results in deubiquitination by USP36 and thus decreased degradation, and (C) illustrates another oncogenic mechanism of EZH2 in extranodal NKTL through JAK3 phosphorylation and subsequent transcription activation. This indicates that both JAK3 and MELK are potential targets for arresting EZH2 oncogenesis in extranodal NKTL. SET, Su(var)3-9, enhancer-of-zeste and trithorax.