The EMT Modulator SNAI1 Contributes to AML Pathogenesis Via Its Interaction with LSD1

Overview

Journal Blood

Publisher Elsevier

Specialty Hematology

Date 2020 May 6

PMID 32369597

Citations 28

Authors

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 N Q Vo

Yizhou Huang

Kathy Knezevic

William R L McInnes

Benjamin J Shields

Helen Mitchell

Matthew E Ritchie

Tim Lammens

Beatrice Lintermans

Pieter Van Vlierberghe

Nicholas C Wong

Katharina Haigh

Julie A I Thoms

Emma Toulmin

David J Curtis

Ethan P Oxley

Ross A Dickins

Dominik Beck

Andrew Perkins

Matthew P McCormack

Melissa J Davis

Geert Berx

Johannes Zuber

John E Pimanda

Benjamin T Kile

Steven Goossens

Jody J Haigh

Affiliations

Soon will be listed here.

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.

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