Journal article
Deletion of the transcriptional regulator TFAP4 accelerates c-MYC-driven lymphomagenesis
MA Potts, S Mizutani, AL Garnham, CSN Li Wai Suen, AJ Kueh, L Tai, M Pal, A Strasser, MJ Herold
Cell Death and Differentiation | SPRINGERNATURE | Published : 2023
Abstract
Many lymphoid malignancies arise from deregulated c-MYC expression in cooperation with additional genetic lesions. While many of these cooperative genetic lesions have been discovered and their functions characterised, DNA sequence data of primary patient samples suggest that many more do exist. However, the nature of their contributions to c-MYC driven lymphomagenesis have not yet been investigated. We identified TFAP4 as a potent suppressor of c-MYC driven lymphoma development in a previous genome-wide CRISPR knockout screen in primary cells in vivo [1]. CRISPR deletion of TFAP4 in Eµ-MYC transgenic haematopoietic stem and progenitor cells (HSPCs) and transplantation of these manipulated H..
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Awarded by University of Melbourne
Funding Acknowledgements
The authors thank the WEHI screening lab for providing arrayed glycerol stocks of sgRNAs; Dr S. Wilcox for performing NGS; Drs S. Nutt and A. Kallies for insightful discussions. We thank the WEHI Bioservices staff D. Fayle, G. Siciliano, C. Epifanio and C. Gatt for animal care and husbandry; T. Nikolaou for irradiation of mice and ADVIA services; the WEHI core facilities for help with Flow Cytometry and Bioinformatics support and our colleagues in the Herold, Strasser and Kelly laboratories for advice and support with experiments. This work was supported by grants and fellowships from the Australian National Health and Medical Research Council (NHMRC) (Project Grants 1159658, 1186575, 1143105,1145728 to MJH and AS, Ideas Grants Program Grant 1113133 to AS Fellowship 1020363 to AS, 1156095 to MJH), the Leukemia and Lymphoma Society of America (LLS SCOR 7015-18 to AS and MJH), the Cancer Council of Victoria (project grant 1147328 and 2021 Grant In Aid to MJH, 1052309 to AS~and Venture Grant to MJH and AS), Phenomics Australia (to AJK and MJH). MAP is supported by an Australian Government Research Training Program Scholarship provided by the Australian Commonwealth Government and the University of Melbourne. SM was supported by the Uehara Memorial Foundation and JSPS Grant-in-Aid for Research Activity Start-up (20K22854). This project was supported by operational infrastructure grants through the Australian Government Independent Research Institute Infrastructure Support Scheme (361646 and 9000220) and the Victorian State Government Operational Infrastructure Support Program.