Journal article

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

Catherine L Carmichael, Jueqiong Wang, Thao Nguyen, Oluseyi Kolawole, Aissa Benyoucef, Charlotte De Maziere, Anna R Milne, Sona Samuel, Kevin Gillinder, Soroor Hediyeh-zadeh, Anh NQ Vo, Yizhou Huang, Kathy Knezevic, William RL McInnes, Benjamin J Shields, Helen Mitchell, Matthew E Ritchie, Tim Lammens, Beatrice Lintermans, Pieter Van Vlierberghe Show all

Blood | AMER SOC HEMATOLOGY | Published : 2020


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 ..

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Awarded by Independent Research Institutes Infrastructure Support Scheme from the Australian National Health and Medical Research Council

Awarded by Canadian Institute of Health Research

Awarded by Div Of Industrial Innovation & Partnersh

Funding Acknowledgements

This work was supported by the Multi-modal Australian Sciences Imaging and Visualisation Environment high-performance computing facility and National eResearch Collaboration Tools and Resources project and funded by project grants G1141081 (J.J.H.); 1102589, 1139787, 11398111, and 1160110 (J.E. P.); program grants 1016647 and 1113577 (B.T.K.), and Senior Research Fellowship (D.J.C) and Independent Research Institutes Infrastructure Support Scheme grant 361646 (B.T.K.) from the Australian National Health and Medical Research Council. T.L. received funding from vzw Kinderkankerfonds and D.B. received funding from Cancer Institute NSW. J.J.H. also received funding from the Canadian Institute of Health Research (project grant 419220). S.G. and P.V.V. received funding from the European Hematology Association (EHA), the Research Foundation Flanders (FWO), the Basic Research Fund of Ghent University and the Belgian Foundation Against Cancer. J.E.P. is also supported by the Anthony Rothe Leukemia Foundation, Translational Cancer Research Network, Cancer Institute NSW, NSW Health Pathology, and South Eastern Area Laboratory Services.