Super-Enhancer-Driven TOX2 Mediates Oncogenesis in Natural Killer/T Cell Lymphoma

Background: Extranodal natural killer/T-cell lymphoma (NKTL) is an EBV associated, aggressive malignancy. Activation of JAK/STAT pathway, overexpression of EZH2, and alternations in epigenetic program have been implicated in the pathogenesis of NKTL. Combined chemotherapy-radiotherapy is standard treatment for NKTL patients, but often associated with high relapse rate and serious side effects. New drugs, including anti-PD1 antibody pembrolizumab, have been explored. Overall, treatment for NKTL patients remains challenge in clinic. Super-enhancers (SEs) are defined as large clusters of cis-acting enhancers, marked by high level bindings of acetylation of histone H3 lysine 27 (H3K27ac), coactivators and transcription factors. SE associated oncogenes have been demonstrated to play key roles in various types of cancers. In this study, we aim to define the SE landscapes of NKTL for a better understanding of the molecular pathogenesis of NKTL and to identify novel therapeutic targets.