BCOR and BCORL1 Mutations Drive Epigenetic Reprogramming and Oncogenic Signaling by Unlinking PRC1.1 from Target Genes.
Eva J SchaeferHelen C WangHannah Q KarpClifford A MeyerPaloma CejasMicah D GearhartEmmalee R AdelmanIman FaresAnnie ApffelKlothilda LimYingtian XieChristopher J GibsonMonica SchenoneH Moses MurdockEunice S WangLukasz P GondekMartin P CarrollRahul S VedulaEric S WinerJacqueline S GarciaRichard M StoneMarlise R LuskinSteven A CarrHenry W LongVivian J BardwellMaria E FigueroaR Coleman LindsleyPublished in: Blood cancer discovery (2022)
We demonstrate that BCOR and BCORL1 mutations in leukemia unlink PRC1.1 repressive function from target genes, resulting in epigenetic reprogramming and activation of aberrant cell signaling programs that mediate treatment resistance. Our study provides mechanistic insights into the pathogenesis of PRC1.1-mutated leukemia that inform novel therapeutic approaches. This article is highlighted in the In This Issue feature, p. 85.