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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Bibliographic Details
Published in:Scientific reports 2016-10, Vol.6 (1), p.34957-34957, Article 34957
Main Authors: Saia, Marco, Termanini, Alberto, Rizzi, Nicoletta, Mazza, Massimiliano, Barbieri, Elisa, Valli, Debora, Ciana, Paolo, Gruszka, Alicja M., Alcalay, Myriam
Format: Article
Language:English
Subjects:
631/80/84/2176
692/4028/67/1990/283/1897
692/4028/67/395
Adhesion
AML1 protein
Binding sites
Bone marrow
Cell adhesion
Cell adhesion & migration
Cell migration
Deoxyribonucleic acid
DNA
ETO protein
Fusion protein
Hematopoietic stem cells
Humanities and Social Sciences
multidisciplinary
Myelodysplastic syndrome
Pluripotency
Progenitor cells
Ribonucleic acid
RNA
Science
Stromal cells
Transcription
Transplantation
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Summary: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.
ISSN:2045-2322
2045-2322
DOI:10.1038/srep34957