Research Publications

Back

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
2020-05-05
Blood
Journal epub ahead of print
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.
ASH
Bioinformatics; Epigenetics and Development
10.1182/blood.2019002548
32369597
Refer to copyright notice on published article.

Back
Creation Date 2020-05-18 11:15:14 Last Modified 2020-05-18 11:22:32