biostudies-literatureDanis ENCATS NIH HHSNHLBI NIH HHSNational Heart, Lung, and Blood Institute, Bethesda, MDNCI NIH HHSChildren's Hospital Colorado Research Institute930-935.e6https://www.ebi.ac.uk/biostudies/studies/S-EPMC4630114biostudies-literatureUnknown43(11)Polycomb repressive complex 2 (PRC2) is a chromatin regulator with central roles in development and cancer. The canonical function of PRC2 is the trimethylation of histone 3 on lysine residue 27. This epigenetic modification is associated with gene silencing. Both tumor suppressor and oncogenic functions have been reported for PRC2, depending on cellular context. In leukemia mediated by the leukemogenic fusion MLL-AF9, complete ablation of canonical PRC2 function by genetic inactivation of the core component embryonic ectoderm development (Eed) or by combined pharmacologic inhibition of the PRC2 methyltransferases EZH2 and EZH1 has a strong anti-leukemic effect, and this effect has been linked to de-repression of the PRC2 target locus Cdkn2a. We asked whether inactivation of Cdkn2a is suffExperimental hematologyInactivation of Eed impedes MLL-AF9-mediated leukemogenesis through Cdkn2a-dependent and Cdkn2a-independent mechanisms in a murine model.PMC4630114National Cancer Institute, Bethesda, MD P30CA046934K08HL102264P30 CA046934K08 CA154777P30CA046934P30 CA008748NCI K08CA154777K08CA154777K08 HL102264UL1 TR001082Zhu NArmstrong SAYamauchi THaladyna JNeff TBernt KMXie HRiedel SEchanique KOrkin SHDanis EKalkur RfalseInactivation of Eed impedes MLL-AF9-mediated leukemogenesis through Cdkn2a-dependent and Cdkn2a-independent mechanisms in a murine model.Polycomb repressive complex 2 (PRC2) is a chromatin regulator with central roles in development and cancer. The canonical function of PRC2 is the trimethylation of histone 3 on lysine residue 27. This epigenetic modification is associated with gene silencing. Both tumor suppressor and oncogenic functions have been reported for PRC2, depending on cellular context. In leukemia mediated by the leukemogenic fusion MLL-AF9, complete ablation of canonical PRC2 function by genetic inactivation of the core component embryonic ectoderm development (Eed) or by combined pharmacologic inhibition of the PRC2 methyltransferases EZH2 and EZH1 has a strong anti-leukemic effect, and this effect has been linked to de-repression of the PRC2 target locus Cdkn2a. We asked whether inactivation of Cdkn2a is suff2015-01-01T00:00:00Z2015 Nov2026-05-05T09:57:07.924Z2019-03-27T02:01:12ZS-EPMC46301142611850210.1016/j.exphem.2015.06.005