Please use this identifier to cite or link to this item: https://hdl.handle.net/2440/132020
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Type: Journal article
Title: The EMT modulator SNAI1 contributes to AML pathogenesis via its interaction with LSD1
Author: Carmichael, C.L.
Wang, J.
Nguyen, T.
Kolawole, O.
Benyoucef, A.
De Mazière, C.
Milne, A.R.
Samuel, S.
Gillinder, K.
Hediyeh-Zadeh, S.
Vo, A.N.Q.
Huang, Y.
Knezevic, K.
McInnes, W.R.L.
Shields, B.J.
Mitchell, H.
Ritchie, M.E.
Lammens, T.
Lintermans, B.
Van Vlierberghe, P.
et al.
Citation: Blood, 2020; 136(8):957-973
Publisher: American Society of Hematology
Issue Date: 2020
ISSN: 0006-4971
1528-0020
Statement of
Responsibility: 
Catherine L. Carmichael ... Benjamin T. Kile ... et al.
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.
Keywords: Protein binding
Rights: © 2020 by The American Society of Hematology
DOI: 10.1182/blood.2019002548
Grant ID: http://purl.org/au-research/grants/nhmrc/GNT1141081
http://purl.org/au-research/grants/nhmrc/1102589
http://purl.org/au-research/grants/nhmrc/1139787
http://purl.org/au-research/grants/nhmrc/1139811
http://purl.org/au-research/grants/nhmrc/GNT1160110
http://purl.org/au-research/grants/nhmrc/1016647
http://purl.org/au-research/grants/nhmrc/1113577
http://purl.org/au-research/grants/nhmrc/361646
Appears in Collections:Medicine publications

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