Identification and Targeting of the Developmental Blockade in Extranodal Natural Killer/T-cell Lymphoma.
Bethany L Mundy-BosseChristoph WeigelYue-Zhong WuSalma AbdelbakyYoussef YoussefSusana Beceiro CasasNicholas PolleyGabrielle ErnstKaren A YoungKathleen K McConnellAnsel P NalinKevin G WuMegan BroughtonMatthew R LordoEkaterina AltynovaEverardo Hegewisch-SolloaDaniel Y Enriquez-VeraDaniela DueñasCarlos BarrionuevoShan-Chi YuAtif SaleemCarlos J SuarezEdward L BriercheckHernan Molina-KirschThomas P LoughranDieter WeichenhanChristoph PlassJohn C ReneauEmily M MaceFabiola Valvert GamboaDavid M WeinstockYasodha NatkunamMichael A CaligiuriAnjali MishraPierluigi PorcuRobert A BaiocchiJonathan E BrammerAharon G FreudChristopher C OakesPublished in: Blood cancer discovery (2022)
Through epigenetic and transcriptomic analyses of ENKTL, a rare, aggressive malignancy, along with normal NK-cell developmental intermediates, we identified that extreme DNA hypermethylation targets genes required for NK-cell development. Disrupting this epigenetic blockade in novel PDX models led to ENKTL differentiation and improved survival. This article is highlighted in the In This Issue feature, p. 85.