Contrasting requirements during disease evolution identify EZH2 as a therapeutic target in AML

Basheer, Faisal; Giotopoulos, George; Meduri, Eshwar; Yun, Hayang; Mazan, Milena; Sasca, Daniel; Gallipoli, Paolo; Marando, Ludovica; Asby, Ryan; Sheppard, Olivia; Vassiliou, George; Huntly, Brian

Contrasting requirements during disease evolution identify EZH2 as a therapeutic target in AML

Published version

Peer-reviewed

Repository URI

https://www.repository.cam.ac.uk/handle/1810/290577

Repository DOI

https://doi.org/10.17863/CAM.37804

Files

Published version (2.79 MB)

Type

Article

Authors

Basheer, Faisal

Giotopoulos, George

https://orcid.org/0000-0003-1390-6592

Meduri, Eshwar

Yun, Hayang

Mazan, Milena

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Abstract

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 target

Keywords

StemCellInstitute

Journal Title

Journal of Experimental Medicine

Journal ISSN

1540-9538
1540-9538

Volume Title

216

Publisher

Rockefeller University Press

Publisher DOI

https://doi.org/10.1084/jem.20181276

Rights

Attribution 4.0 International

Sponsorship

European Research Council (647685)
Cancer Research UK (25508)
Academy of Medical Sciences (unknown)
Lady Tata Memorial Trust (unknown)
Wellcome Trust (109967/Z/15/Z)
Wellcome Trust (097922/Z/11/Z)
Wellcome Trust (100140/Z/12/Z)
Medical Research Council (MC_PC_12009)
Medical Research Council (MR/R009708/1)

The 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 interests.

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Cambridge University Research Outputs