Journal article

HBO1 is required for the maintenance of leukaemia stem cells

Laura MacPherson, Juliana Anokye, Miriam M Yeung, Enid YN Lam, Yih-Chih Chan, Chen-Fang Weng, Paul Yeh, Kathy Knezevic, Miriam S Butler, Annabelle Hoegl, Kah-Lok Chan, Marian L Burr, Linden J Gearing, Tracy Willson, Joy Liu, Jarny Choi, Yuqing Yang, Rebecca A Bilardi, Hendrik Falk, Nguyen Nghi Show all

Nature | NATURE PUBLISHING GROUP | Published : 2020

Abstract

Acute myeloid leukaemia (AML) is a heterogeneous disease characterized by transcriptional dysregulation that results in a block in differentiation and increased malignant self-renewal. Various epigenetic therapies aimed at reversing these hallmarks of AML have progressed into clinical trials, but most show only modest efficacy owing to an inability to effectively eradicate leukaemia stem cells (LSCs)1. Here, to specifically identify novel dependencies in LSCs, we screened a bespoke library of small hairpin RNAs that target chromatin regulators in a unique ex vivo mouse model of LSCs. We identify the MYST acetyltransferase HBO1 (also known as KAT7 or MYST2) and several known members of the HB..

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Grants

Awarded by National Health and Medical Research Council of Australia


Awarded by Novo Nordisk Foundation Hallas Moller Fellowship


Awarded by Novo Nordisk Foundation


Funding Acknowledgements

We thank C. Lovitt, J. Wingerd, S. Jackson and E. Allan for their technical contributions to this project. The work in the Dawson, Blewitt and Burns laboratories was supported by the Cancer Council Victoria Venture Grant Scheme, and Dawson laboratory work was supported by project grant funding from the National Health and Medical Research Council of Australia (1085015). We thank the following funders for fellowship and grant support: Leukaemia Foundation Australia senior fellowship, Cancer Council Victoria Dunlop Fellopship and Howard Hughes Medical Institute international research scholarship (M.A.D.); Victoria Cancer Agency early-career (L.M.) and mid-career (E.Y.N.L.) fellowships; CSL Centenary fellowship (S.-J.D.), Snowdome Foundation (P.Y.), Maddie Riewoldt's Vision Foundation (Y.-C.C.), Bellberry-Viertel Senior Medical Research Fellowship (M.E.B), Novo Nordisk Foundation Hallas Moller Fellowship NNF14OC0008541 (C.C.), National Health and Medical Research Council of Australia through project grants 1081421 (J.B.B. and T.T.), 575558, 1084248 (A.K.V. and T.T.), research fellowship 1081421 (A.K.V.) and postgraduate scholarship (K.-L.C.). Salary support for M.Z., M.d.S., H.F., C.C., P.S.K., P.A.S., I.P.S. and B.J.M. was provided by the Cancer Therapeutics CRC, funded through the Australian Government's Cooperative Research Centre programme. The Novo Nordisk Foundation Center for Protein Research is supported financially by the Novo Nordisk Foundation (grant agreement NNF14CC0001). This work was made possible through the Victorian State Government Operation Infrastructure Support and Australian National Health and the Medical Research Council Research Institute Infrastructure Support Scheme. We thank the Australian Synchrotron and beamline scientists for help with data collection; this research was undertaken in part using the MX2 beamline at the Australian Synchrotron and made use of the ACRF detector.