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Contrasting requirements during disease evolution identify EZH2 as a therapeutic target in AML
This study demonstrates that EZH2 has stage-specific and diametrically opposite roles during the induction and maintenance stages of AML. However, different transcriptional programs are affected at each stage, identifying mutant EZH2 as a prognostic marker and paradoxically wild-type EZH2 as a potential therapeutic targetThe Huntly laboratory is funded by CRUK (Programme C18680/A25508), ERC (Grant 647685 COMAL), KKLF, MRC, Bloodwise, the Wellcome Trust (WT) and the Cambridge NIHR BRC. F.B. is a recipient of a Wellcome Trust PhD for Clinicians award. P.G. is funded by the Wellcome Trust (109967/Z/15/Z). We acknowledge the WT/MRC centre grant (097922/Z/11/Z) and support from WT strategic award 100140. Research in the laboratory is also supported by core funding from Wellcome and MRC to the Wellcome-MRC Cambridge Stem Cell Institute. We are grateful to Chiara Cossetti, Gabriela Grondys-Kotarba and Reiner Schulte at the CIMR Flow Cytometry Core for their invaluable help and advice with cell sorting. This research was supported by the Cambridge NIHR BRC Cell Phenotyping Hub. Patient samples were received from the UK NCRI AML trials. The authors declare no competing financial
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