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

Marco Saia, Alberto Termanini, Nicoletta Rizzi, Massimiliano Mazza, Elisa Barbieri, Debora Valli, Paolo Ciana, Alicja M. Gruszka, Myriam Alcalay

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish
Article number34957
JournalScientific Reports
Volume6
DOIs
Publication statusPublished - Oct 7 2016

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Hematopoietic Stem Cells
Cell Adhesion
Cell Movement
Preleukemia
RNA Sequence Analysis
Co-Repressor Proteins
Pluripotent Stem Cells
Stromal Cells
Acute Myeloid Leukemia
Disease Progression
Transplantation
Bone Marrow
Binding Sites
Phenotype
Cell Line
DNA
Genes
Proteins

ASJC Scopus subject areas

  • General

Cite this

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.

In: Scientific Reports, Vol. 6, 34957, 07.10.2016.

Research output: Contribution to journalArticle

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AU - Saia, Marco

AU - Termanini, Alberto

AU - Rizzi, Nicoletta

AU - Mazza, Massimiliano

AU - Barbieri, Elisa

AU - Valli, Debora

AU - Ciana, Paolo

AU - Gruszka, Alicja M.

AU - Alcalay, Myriam

PY - 2016/10/7

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AB - 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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