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AML1/ETO accelerates cell migration and impairs cell-to-cell adhesion and homing of hematopoietic stem/progenitor cells

The AML1/ETO fusion protein found in acute myeloid leukemias functions as a transcriptional regulator by recruiting co-repressor complexes to its DNA binding site. In order to extend the understanding of its role in preleukemia, we expressed AML1/ETO in a murine immortalized pluripotent hematopoieti...

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Autores principales: Saia, Marco, Termanini, Alberto, Rizzi, Nicoletta, Mazza, Massimiliano, Barbieri, Elisa, Valli, Debora, Ciana, Paolo, Gruszka, Alicja M., Alcalay, Myriam
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5054523/
https://www.ncbi.nlm.nih.gov/pubmed/27713544
http://dx.doi.org/10.1038/srep34957
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author Saia, Marco
Termanini, Alberto
Rizzi, Nicoletta
Mazza, Massimiliano
Barbieri, Elisa
Valli, Debora
Ciana, Paolo
Gruszka, Alicja M.
Alcalay, Myriam
author_facet Saia, Marco
Termanini, Alberto
Rizzi, Nicoletta
Mazza, Massimiliano
Barbieri, Elisa
Valli, Debora
Ciana, Paolo
Gruszka, Alicja M.
Alcalay, Myriam
author_sort Saia, Marco
collection PubMed
description The AML1/ETO fusion protein found in acute myeloid leukemias functions as a transcriptional regulator by recruiting co-repressor complexes to its DNA binding site. In order to extend the understanding of its role in preleukemia, we expressed AML1/ETO in a murine immortalized pluripotent hematopoietic stem/progenitor cell line, EML C1, and found that genes involved in functions such as cell-to-cell adhesion and cell motility were among the most significantly regulated as determined by RNA sequencing. In functional assays, AML1/ETO-expressing cells showed a decrease in adhesion to stromal cells, an increase of cell migration rate in vitro, and displayed an impairment in homing and engraftment in vivo upon transplantation into recipient mice. Our results suggest that AML1/ETO expression determines a more mobile and less adherent phenotype in preleukemic cells, therefore altering the interaction with the hematopoietic niche, potentially leading to the migration across the bone marrow barrier and to disease progression.
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spelling pubmed-50545232016-10-19 AML1/ETO accelerates cell migration and impairs cell-to-cell adhesion and homing of hematopoietic stem/progenitor cells Saia, Marco Termanini, Alberto Rizzi, Nicoletta Mazza, Massimiliano Barbieri, Elisa Valli, Debora Ciana, Paolo Gruszka, Alicja M. Alcalay, Myriam Sci Rep Article The AML1/ETO fusion protein found in acute myeloid leukemias functions as a transcriptional regulator by recruiting co-repressor complexes to its DNA binding site. In order to extend the understanding of its role in preleukemia, we expressed AML1/ETO in a murine immortalized pluripotent hematopoietic stem/progenitor cell line, EML C1, and found that genes involved in functions such as cell-to-cell adhesion and cell motility were among the most significantly regulated as determined by RNA sequencing. In functional assays, AML1/ETO-expressing cells showed a decrease in adhesion to stromal cells, an increase of cell migration rate in vitro, and displayed an impairment in homing and engraftment in vivo upon transplantation into recipient mice. Our results suggest that AML1/ETO expression determines a more mobile and less adherent phenotype in preleukemic cells, therefore altering the interaction with the hematopoietic niche, potentially leading to the migration across the bone marrow barrier and to disease progression. Nature Publishing Group 2016-10-07 /pmc/articles/PMC5054523/ /pubmed/27713544 http://dx.doi.org/10.1038/srep34957 Text en Copyright © 2016, The Author(s) http://creativecommons.org/licenses/by/4.0/ This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/
spellingShingle Article
Saia, Marco
Termanini, Alberto
Rizzi, Nicoletta
Mazza, Massimiliano
Barbieri, Elisa
Valli, Debora
Ciana, Paolo
Gruszka, Alicja M.
Alcalay, Myriam
AML1/ETO accelerates cell migration and impairs cell-to-cell adhesion and homing of hematopoietic stem/progenitor cells
title AML1/ETO accelerates cell migration and impairs cell-to-cell adhesion and homing of hematopoietic stem/progenitor cells
title_full AML1/ETO accelerates cell migration and impairs cell-to-cell adhesion and homing of hematopoietic stem/progenitor cells
title_fullStr AML1/ETO accelerates cell migration and impairs cell-to-cell adhesion and homing of hematopoietic stem/progenitor cells
title_full_unstemmed AML1/ETO accelerates cell migration and impairs cell-to-cell adhesion and homing of hematopoietic stem/progenitor cells
title_short AML1/ETO accelerates cell migration and impairs cell-to-cell adhesion and homing of hematopoietic stem/progenitor cells
title_sort aml1/eto accelerates cell migration and impairs cell-to-cell adhesion and homing of hematopoietic stem/progenitor cells
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5054523/
https://www.ncbi.nlm.nih.gov/pubmed/27713544
http://dx.doi.org/10.1038/srep34957
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