Patterson, Shaun D. and Massett, Matthew E. and Huang, Xu and Jørgensen, Heather G. and Michie, Alison M. (2024) The MYC–NFATC2 axis maintains the cell cycle and mitochondrial function in acute myeloid leukaemia cells. Molecular Oncology, 18 (9). pp. 2234-2254. ISSN 1574-7891
AI Summary:
The study identifies a novel therapeutic target, histone lysine demethylase 4A (KDM4A), in acute myeloid leukaemia (AML). The study also shows that KDM4A regulates the transcription factor nuclear factor of activated T cells 2 (NFATC2) and its downstream targets.AI Topics:
Acute myeloid leukaemia (AML) is a clonal haematological malignancy affecting the myeloid lineage, with generally poor patient outcomes owing to the lack of targeted therapies. The histone lysine demethylase 4A (KDM4A) has been established as a novel therapeutic target in AML, due to its selective oncogenic role within leukaemic cells. We identify that the transcription factor nuclear factor of activated T cells 2 (NFATC2) is a novel binding and transcriptional target of KDM4A in the human AML THP-1 cell line. Furthermore, cytogenetically diverse AML cell lines, including THP-1, were dependent on NFATC2 for colony formation in vitro, highlighting a putative novel mechanism of AML oncogenesis. Our study demonstrates that NFATC2 maintenance of cell cycle progression in human AML cells was driven primarily by CCND1. Through RNA sequencing (RNA-seq) and chromatin immunoprecipitation sequencing (ChIP-seq), NFATc2 was shown to bind to the promoter region of genes involved in oxidative phosphorylation and subsequently regulate their gene expression in THP-1 cells. Furthermore, our data show that NFATC2 shares transcriptional targets with the transcription factor c-MYC, with MYC knockdown phenocopying NFATC2 knockdown. These data suggest a newly identified co-ordinated role for NFATC2 and MYC in the maintenance of THP-1 cell function, indicative of a potential means of therapeutic targeting in human AML.
Patterson, Shaun D.
Author
Samarakoon, Youhan and Yelland, Tamas and Garcia-Gonzalez, Esther and Justo-Junior, Amauri da Silva and Mahmood, Mahnoor and Manoharan, Anand and Patterson, Shaun and Serafin, Valentina and Gammage, Payam A. and Marmiroli, Sandra and Halsey, Christina and Ismail, Shehab and Roberts, Edward W. (2025) UNC119 regulates T-cell receptor signalling in primary T cells and T acute lymphocytic leukaemia. Life Science Alliance, 8 (3): e202403066. ISSN 2575-1077
Patterson, Shaun D. and Massett, Matthew E. and Huang, Xu and Jørgensen, Heather G. and Michie, Alison M. (2024) The MYC–NFATC2 axis maintains the cell cycle and mitochondrial function in acute myeloid leukaemia cells. Molecular Oncology, 18 (9). pp. 2234-2254. ISSN 1574-7891
See full publications listMassett, Matthew E.
Author
Patterson, Shaun D. and Massett, Matthew E. and Huang, Xu and Jørgensen, Heather G. and Michie, Alison M. (2024) The MYC–NFATC2 axis maintains the cell cycle and mitochondrial function in acute myeloid leukaemia cells. Molecular Oncology, 18 (9). pp. 2234-2254. ISSN 1574-7891
See full publications listHuang, Xu
Author
Patterson, Shaun D. and Massett, Matthew E. and Huang, Xu and Jørgensen, Heather G. and Michie, Alison M. (2024) The MYC–NFATC2 axis maintains the cell cycle and mitochondrial function in acute myeloid leukaemia cells. Molecular Oncology, 18 (9). pp. 2234-2254. ISSN 1574-7891
See full publications listJorgensen, Heather G.
Author
Patterson, Shaun D. and Massett, Matthew E. and Huang, Xu and Jørgensen, Heather G. and Michie, Alison M. (2024) The MYC–NFATC2 axis maintains the cell cycle and mitochondrial function in acute myeloid leukaemia cells. Molecular Oncology, 18 (9). pp. 2234-2254. ISSN 1574-7891
Ramirez-Guzman, Lizbeth A. and Huang, Wenjing and Cole, John J. and Jorgensen, Heather G. (2024) GAS2 upregulation is a targetable vulnerability in chronic myeloid leukaemia. International Journal of Translational Medicine, 4 (2). pp. 354-368. ISSN 2673-8937
Scott, Mary T. and Liu, Wei and Mitchell, Rebecca and Clarke, Cassie J. and Kinstrie, Ross and Warren, Felix and Almasoudi, Hassan and Stevens, Thomas and Dunn, Karen and Pritchard, John and Drotar, Mark E. and Michie, Alison M. and Jorgensen, Heather G. and Higgins, Brian and Copland, Mhairi and Vetrie, David (2024) Activating p53 abolishes self-renewal of quiescent leukaemic stem cells in residual CML disease. Nature Communications, 15: 651. ISSN 2041-1723
See full publications listMichie, Alison M.
Author
Omar, Ramla and Lee, Michelle A.W. and Gonzalez-Trueba, Laura and Thomson, Cameron R. and Hansen, Uwe and Lianos, Spyridonas and Hazarika, Snoopy and El Abdallah, Omar and Ammar, Malak A. and Cassels, Jennifer and Michie, Alison M. and Bulleid, Neil J. and Malfait, Fransiska and Van Agtmael, Tom (2025) The chemical chaperone 4-phenylbutyric acid rescues molecular cell defects of COL3A1 mutations that cause vascular Ehlers Danlos Syndrome. Cell Death Discovery, 11 (1): 200. ISSN 2058-7716
Patterson, Shaun D. and Massett, Matthew E. and Huang, Xu and Jørgensen, Heather G. and Michie, Alison M. (2024) The MYC–NFATC2 axis maintains the cell cycle and mitochondrial function in acute myeloid leukaemia cells. Molecular Oncology, 18 (9). pp. 2234-2254. ISSN 1574-7891
Donnelly, Hannah and Ross, Ewan and Xiao, Yinbo and Hermantara, Rio and Taqi, Aqeel and Doherty-Boyd, W. Sebastian and Cassels, Jennifer and Tsimbouri, Penelope M. and Dunne, Karen M. and Hay, Jodie and Cheng, Annie and Meek, R.M. Dominic and Jain, Nikhil and West, Christopher and Wheadon, Helen and Michie, Alison M. and Peault, Bruno and West, Adam G. and Salmeron-Sanchez, Manuel and Dalby, Matthew J. (2024) Bioengineered niches that recreate physiological extracellular matrix organisation to support long-term haematopoietic stem cells. Nature Communications, 15: 5791. ISSN 2041-1723
See full publications listAvailable under License Creative Commons Attribution.
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