The EMT modulator SNAI1 contributes to AML pathogenesis via its interaction with LSD1.

Carmichael, CL; Wang, J; Nguyen, T; Kolawole, O; Benyoucef, A; De Mazière, C; Milne, AR; Samuel, S; Gillinder, K; Hediyeh-Zadeh, S; Vo, ANQ; Huang, Y; Knezevic, K; McInnes, WRL; Shields, BJ; Mitchell, H; Ritchie, ME; Lammens, T; Lintermans, B; Van Vlierberghe, P; Wong, NC; Haigh, K; Thoms, JAI; Toulmin, E; Curtis, DJ; Oxley, EP; Dickins, RA; Beck, D; Perkins, A; McCormack, MP; Davis, MJ; Berx, G; Zuber, J; Pimanda, JE; Kile, BT; Goossens, S; Haigh, JJ

The EMT modulator SNAI1 contributes to AML pathogenesis via its interaction with LSD1.

Carmichael, CL Wang, J Nguyen, T Kolawole, O Benyoucef, A De Mazière, C Milne, AR Samuel, S Gillinder, K Hediyeh-Zadeh, S Vo, ANQ Huang, Y

Knezevic, K McInnes, WRL Shields, BJ Mitchell, H Ritchie, ME Lammens, T Lintermans, B Van Vlierberghe, P Wong, NC Haigh, K Thoms, JAI Toulmin, E Curtis, DJ Oxley, EP Dickins, RA Beck, D Perkins, A McCormack, MP Davis, MJ Berx, G Zuber, J Pimanda, JE Kile, BT Goossens, S Haigh, JJ

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Publisher:: AMER SOC HEMATOLOGY
Publication Type:: Journal Article
Citation:: Blood, 2020, 136, (8), pp. 957-973
Issue Date:: 2020-08

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Field	Value	Language
dc.contributor.author	Carmichael, CL
dc.contributor.author	Wang, J
dc.contributor.author	Nguyen, T
dc.contributor.author	Kolawole, O
dc.contributor.author	Benyoucef, A
dc.contributor.author	De Mazière, C
dc.contributor.author	Milne, AR
dc.contributor.author	Samuel, S
dc.contributor.author	Gillinder, K
dc.contributor.author	Hediyeh-Zadeh, S
dc.contributor.author	Vo, ANQ
dc.contributor.author	Huang, Y https://orcid.org/0000-0002-7003-3110
dc.contributor.author	Knezevic, K
dc.contributor.author	McInnes, WRL
dc.contributor.author	Shields, BJ
dc.contributor.author	Mitchell, H
dc.contributor.author	Ritchie, ME
dc.contributor.author	Lammens, T
dc.contributor.author	Lintermans, B
dc.contributor.author	Van Vlierberghe, P
dc.contributor.author	Wong, NC
dc.contributor.author	Haigh, K
dc.contributor.author	Thoms, JAI
dc.contributor.author	Toulmin, E
dc.contributor.author	Curtis, DJ
dc.contributor.author	Oxley, EP
dc.contributor.author	Dickins, RA
dc.contributor.author	Beck, D
dc.contributor.author	Perkins, A
dc.contributor.author	McCormack, MP
dc.contributor.author	Davis, MJ
dc.contributor.author	Berx, G
dc.contributor.author	Zuber, J
dc.contributor.author	Pimanda, JE
dc.contributor.author	Kile, BT
dc.contributor.author	Goossens, S
dc.contributor.author	Haigh, JJ
dc.date.accessioned	2021-03-05T03:22:00Z
dc.date.available	2020-04-15
dc.date.available	2021-03-05T03:22:00Z
dc.date.issued	2020-08
dc.identifier.citation	Blood, 2020, 136, (8), pp. 957-973
dc.identifier.issn	0006-4971
dc.identifier.issn	1528-0020
dc.identifier.uri	http://hdl.handle.net/10453/146808
dc.description.abstract	Modulators of epithelial-to-mesenchymal transition (EMT) have recently emerged as novel players in the field of leukemia biology. The mechanisms by which EMT modulators contribute to leukemia pathogenesis, however, remain to be elucidated. Here we show that overexpression of SNAI1, a key modulator of EMT, is a pathologically relevant event in human acute myeloid leukemia (AML) that contributes to impaired differentiation, enhanced self-renewal, and proliferation of immature myeloid cells. We demonstrate that ectopic expression of Snai1 in hematopoietic cells predisposes mice to AML development. This effect is mediated by interaction with the histone demethylase KDM1A/LSD1. Our data shed new light on the role of SNAI1 in leukemia development and identify a novel mechanism of LSD1 corruption in cancer. This is particularly pertinent given the current interest surrounding the use of LSD1 inhibitors in the treatment of multiple different malignancies, including AML.
dc.format	Print
dc.language	eng
dc.publisher	AMER SOC HEMATOLOGY
dc.relation	Cancer Institute NSW
dc.relation	Gilead Sciences Pty Ltd
dc.relation	Anthony Rothe Memorial Trust
dc.relation.ispartof	Blood
dc.relation.isbasedon	10.1182/blood.2019002548
dc.rights	info:eu-repo/semantics/closedAccess
dc.subject	1102 Cardiorespiratory Medicine and Haematology, 1103 Clinical Sciences, 1114 Paediatrics and Reproductive Medicine
dc.subject.classification	Immunology
dc.title	The EMT modulator SNAI1 contributes to AML pathogenesis via its interaction with LSD1.
dc.type	Journal Article
utslib.citation.volume	136
utslib.location.activity	United States
utslib.for	1102 Cardiorespiratory Medicine and Haematology
utslib.for	1103 Clinical Sciences
utslib.for	1114 Paediatrics and Reproductive Medicine
pubs.organisational-group	/University of Technology Sydney/Faculty of Engineering and Information Technology
pubs.organisational-group	/University of Technology Sydney/Strength - CHT - Health Technologies
pubs.organisational-group	/University of Technology Sydney/Strength - AAI - Advanced Analytics Institute Research Centre
pubs.organisational-group	/University of Technology Sydney/Faculty of Engineering and Information Technology/School of Biomedical Engineering
pubs.organisational-group	/University of Technology Sydney
utslib.copyright.status	closed_access	*
pubs.consider-herdc	false
dc.date.updated	2021-03-05T03:21:57Z
pubs.issue	8
pubs.publication-status	Published
pubs.volume	136
utslib.citation.issue	8

Abstract:

Modulators of epithelial-to-mesenchymal transition (EMT) have recently emerged as novel players in the field of leukemia biology. The mechanisms by which EMT modulators contribute to leukemia pathogenesis, however, remain to be elucidated. Here we show that overexpression of SNAI1, a key modulator of EMT, is a pathologically relevant event in human acute myeloid leukemia (AML) that contributes to impaired differentiation, enhanced self-renewal, and proliferation of immature myeloid cells. We demonstrate that ectopic expression of Snai1 in hematopoietic cells predisposes mice to AML development. This effect is mediated by interaction with the histone demethylase KDM1A/LSD1. Our data shed new light on the role of SNAI1 in leukemia development and identify a novel mechanism of LSD1 corruption in cancer. This is particularly pertinent given the current interest surrounding the use of LSD1 inhibitors in the treatment of multiple different malignancies, including AML.

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http://hdl.handle.net/10453/146808