| Literature DB >> 32369597 |
Catherine L Carmichael1, Jueqiong Wang1, Thao Nguyen1, Oluseyi Kolawole1, Aissa Benyoucef2,3, Charlotte De Mazière1,4, Anna R Milne1, Sona Samuel1, Kevin Gillinder1, Soroor Hediyeh-Zadeh5, Anh N Q Vo1, Yizhou Huang6,7, Kathy Knezevic7, William R L McInnes1, Benjamin J Shields1, Helen Mitchell1, Matthew E Ritchie5, Tim Lammens8,9, Beatrice Lintermans9,10, Pieter Van Vlierberghe9,10, Nicholas C Wong1,11, Katharina Haigh1,2,3, Julie A I Thoms12, Emma Toulmin1, David J Curtis1,13, Ethan P Oxley1, Ross A Dickins1, Dominik Beck6,7, Andrew Perkins1, Matthew P McCormack1, Melissa J Davis5,14,15, Geert Berx4,9, Johannes Zuber16, John E Pimanda7,12,17, Benjamin T Kile18, Steven Goossens1,4,9,10,19, Jody J Haigh1,2,3.
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.Entities:
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Year: 2020 PMID： 32369597 PMCID： PMC7441169 DOI： 10.1182/blood.2019002548
Source DB: PubMed Journal: Blood ISSN： 0006-4971 Impact factor: 22.113