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 journalArticlepeer-review

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

ASJC Scopus subject areas

  • General

Fingerprint

Dive into the research topics of 'AML1/ETO accelerates cell migration and impairs cell-to-cell adhesion and homing of hematopoietic stem/progenitor cells'. Together they form a unique fingerprint.

Cite this