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

(2020) BLOOD. 136(8). p.957-973
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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.
Keywords
Immunology, Cell Biology, Biochemistry, Hematology, EXPRESSION, DIFFERENTIATION, PATHWAY, GENES

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MLA
Carmichael, Catherine L., et al. “The EMT Modulator SNAI1 Contributes to AML Pathogenesis via Its Interaction with LSD1.” BLOOD, vol. 136, no. 8, 2020, pp. 957–73, doi:10.1182/blood.2019002548.
APA
Carmichael, C. L., Wang, J., Nguyen, T., Kolawole, O., Benyoucef, A., De Mazière, C., … Haigh, J. J. (2020). The EMT modulator SNAI1 contributes to AML pathogenesis via its interaction with LSD1. BLOOD, 136(8), 957–973. https://doi.org/10.1182/blood.2019002548
Chicago author-date
Carmichael, Catherine L., Jueqiong Wang, Thao Nguyen, Oluseyi Kolawole, Aissa Benyoucef, Charlotte De Mazière, Anna Milne, et al. 2020. “The EMT Modulator SNAI1 Contributes to AML Pathogenesis via Its Interaction with LSD1.” BLOOD 136 (8): 957–73. https://doi.org/10.1182/blood.2019002548.
Chicago author-date (all authors)
Carmichael, Catherine L., Jueqiong Wang, Thao Nguyen, Oluseyi Kolawole, Aissa Benyoucef, Charlotte De Mazière, Anna Milne, Sona Samuel, Kevin Robert Gillinder, Soroor Hediyeh-zadeh, Anh Ngoc Quynh Vo, Yizhou Huang, Kathy Knezevic, William R. L. McInnes, Benjamin J. Shields, Helen Mitchell, Matthew E. Ritchie, Tim Lammens, Béatrice Lintermans, Pieter Van Vlierberghe, Nicholas Wong, Katharina Haigh, Julie A. I. Thoms, Emma Toulmin, David J. Curtis, Ethan P. Oxley, Ross A. Dickins, Dominik Beck, Andrew C Perkins, Matthew P. McCormack, Melissa J. Davis, Geert Berx, Johannes Zuber, John E. Pimanda, Benjamin T. Kile, Steven Goossens, and Jody J. Haigh. 2020. “The EMT Modulator SNAI1 Contributes to AML Pathogenesis via Its Interaction with LSD1.” BLOOD 136 (8): 957–973. doi:10.1182/blood.2019002548.
Vancouver
1.
Carmichael CL, Wang J, Nguyen T, Kolawole O, Benyoucef A, De Mazière C, et al. The EMT modulator SNAI1 contributes to AML pathogenesis via its interaction with LSD1. BLOOD. 2020;136(8):957–73.
IEEE
[1]
C. L. Carmichael et al., “The EMT modulator SNAI1 contributes to AML pathogenesis via its interaction with LSD1,” BLOOD, vol. 136, no. 8, pp. 957–973, 2020.
@article{8661620,
  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.},
  author       = {Carmichael, Catherine L. and Wang, Jueqiong and Nguyen, Thao and Kolawole, Oluseyi and Benyoucef, Aissa and De Mazière, Charlotte and Milne, Anna and Samuel, Sona and Gillinder, Kevin Robert and Hediyeh-zadeh, Soroor and Vo, Anh Ngoc Quynh and Huang, Yizhou and Knezevic, Kathy and McInnes, William R. L. and Shields, Benjamin J. and Mitchell, Helen and Ritchie, Matthew E. and Lammens, Tim and Lintermans, Béatrice and Van Vlierberghe, Pieter and Wong, Nicholas and Haigh, Katharina and Thoms, Julie A. I. and Toulmin, Emma and Curtis, David J. and Oxley, Ethan P. and Dickins, Ross A. and Beck, Dominik and Perkins, Andrew C and McCormack, Matthew P. and Davis, Melissa J. and Berx, Geert and Zuber, Johannes and Pimanda, John E. and Kile, Benjamin T. and Goossens, Steven and Haigh, Jody J.},
  issn         = {0006-4971},
  journal      = {BLOOD},
  keywords     = {Immunology,Cell Biology,Biochemistry,Hematology,EXPRESSION,DIFFERENTIATION,PATHWAY,GENES},
  language     = {eng},
  number       = {8},
  pages        = {957--973},
  title        = {The EMT modulator SNAI1 contributes to AML pathogenesis via its interaction with LSD1},
  url          = {http://dx.doi.org/10.1182/blood.2019002548},
  volume       = {136},
  year         = {2020},
}

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