EZH2-driven immune evasion defines high-risk pediatric AML with t(16;21) FUS::ERG gene fusion.
Nathaniel J ButeynConnor G BurkeVincent J SartoriEve Deering-GardnerZachary J DeBruineDahlya KamarudinDarrell P ChandlerAlexander C MonovichMonika W PerezJoanna S YiRhonda E RiesTodd A AlonzoRussell J H RyanSoheil MeshinchiTimothy J TrichePublished in: bioRxiv : the preprint server for biology (2024)
pAML patients have dismal outcomes. Here we show a ubiquitous immune-evasive phenotype, defined by elevated EZH2 levels and loss of MHC class I and II receptors, present in these patients at diagnosis. Treatment with the EZH2 inhibitor tazemetostat and IFN-γ reverses this phenotype in patient-derived cell lines.