title: AML1/ETO accelerates cell migration and impairs cell-to-cell adhesion and homing of hematopoietic stem/progenitor cells.
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.
authors.affiliation: Department of Experimental Oncology, Istituto Europeo di Oncologia, Via Adamello 16, 20139, Milan, Italy.
authors.forename: Marco
authors.initials: M
authors.lastname: Saia
authors.affiliation: Department of Experimental Oncology, Istituto Europeo di Oncologia, Via Adamello 16, 20139, Milan, Italy.
authors.forename: Alberto
authors.initials: A
authors.lastname: Termanini
authors.affiliation: Department of Pharmacological and Biomolecular Sciences (DiSFeB), University of Milan, Via Balzaretti 9, 20133, Milan, Italy.
authors.forename: Nicoletta
authors.initials: N
authors.lastname: Rizzi
authors.affiliation: Department of Experimental Oncology, Istituto Europeo di Oncologia, Via Adamello 16, 20139, Milan, Italy.
authors.forename: Massimiliano
authors.initials: M
authors.lastname: Mazza
authors.affiliation: Department of Experimental Oncology, Istituto Europeo di Oncologia, Via Adamello 16, 20139, Milan, Italy.
authors.forename: Elisa
authors.initials: E
authors.lastname: Barbieri
authors.affiliation: Department of Experimental Oncology, Istituto Europeo di Oncologia, Via Adamello 16, 20139, Milan, Italy.
authors.forename: Debora
authors.initials: D
authors.lastname: Valli
authors.affiliation: Department of Oncology and Hemato-Oncology, University of Milan, Via Festa del Perdono 7, 20122, Milan, Italy.
authors.forename: Paolo
authors.initials: P
authors.lastname: Ciana
authors.affiliation: Department of Experimental Oncology, Istituto Europeo di Oncologia, Via Adamello 16, 20139, Milan, Italy.
authors.forename: Alicja M
authors.initials: AM
authors.lastname: Gruszka
authors.affiliation: Department of Experimental Oncology, Istituto Europeo di Oncologia, Via Adamello 16, 20139, Milan, Italy.|Department of Oncology and Hemato-Oncology, University of Milan, Via Festa del Perdono 7, 20122, Milan, Italy.
authors.forename: Myriam
authors.initials: M
authors.lastname: Alcalay
mesh_terms: D000818:Animals; D002448:Cell Adhesion / Q000235:genetics / Q000502:physiology; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics / Q000502:physiology; D050676:Core Binding Factor Alpha 2 Subunit / Q000235:genetics / Q000502:physiology; D005260:Female; D006412:Hematopoietic Stem Cells / Q000473:pathology / Q000502:physiology*; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000235:genetics / Q000473:pathology / Q000503:physiopathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D014411:Neoplastic Stem Cells / Q000473:pathology / Q000502:physiology*; D015514:Oncogene Proteins, Fusion / Q000235:genetics / Q000502:physiology*; D000075142:RUNX1 Translocation Partner 1 Protein / Q000235:genetics / Q000502:physiology; D055153:Stem Cell Niche / Q000235:genetics / Q000502:physiology; D059016:Tumor Microenvironment / Q000235:genetics
chemical_list: C107844:AML1-ETO fusion protein, human; C000622500:AML1-ETO fusion protein, mouse; D050676:Core Binding Factor Alpha 2 Subunit; D015514:Oncogene Proteins, Fusion; D000075142:RUNX1 Translocation Partner 1 Protein