The EMT modulator SNAI1 contributes to AML pathogenesis via its interaction with LSD1
- Carmichael, CL; Wang, J; Nguyen, T; Kolawole, O; Benyoucef, A; De Maziere, C; Milne, A; Samuel, S; Gillinder, KR; 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, N; Haigh, K; Thoms, JAI; Toulmin, E; Curtis, DJ; Oxley, EP; Dickins, RA; Beck, D; Perkins, AC; McCormack, MP; Davis, MJ; Berx, G; Zuber, J; Pimanda, JE; Kile, BT; Goossens, S; Haigh, JJ;
Publication Year 2020-05-05, Volume 136, Issue #8, Page 957-973
- Journal Title
- Publication Type
- Journal Article
- 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.
- WEHI Research Division(s)
- Epigenetics And Development; Bioinformatics
- PubMed ID
- Link To PubMed Central Version
- Publisher's Version
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- Refer to copyright notice on published article.
Creation Date: 2020-05-18 11:15:14Last Modified: 2020-10-16 09:12:19