title: Spontaneous cell fusion of acute leukemia cells and macrophages observed in cells with leukemic potential.
abstract: Cell fusion plays a well-recognized physiological role during development, while its function during progression is still unclear. Here, we show that acute myeloid leukemia (AML) cells spontaneously fused with murine host cells in vivo. AML cells fused in most cases with mouse macrophages. Other targets of AML cell fusion were dendritic and endothelial cells. Cytogenetic and molecular analysis revealed that successive recipients conserved detectable amounts of parental DNA. Moreover, in a mouse AML1-ETO model where female AML1-ETO-leukemic cells, expressing CD45.2, were injected in congenic CD45.1 male mice AML cells, we found hybrid cells expressing both allelic types of CD45 and XXY set of sexual chromosomes. More importantly, the fusion protein AML1-ETO was transferred in the hybrid cells. When sorted hybrid cells were reinjected in a secondary recipient, they gave rise to leukemia with 100% penetrance and similar time of onset of leukemic cells. Our data indicate that in vivo fusion of cancer cells with host cells may be a mechanism of gene transfer for cancer dissemination and suggest that fused cells may be used to identify still unrecognized leukemogenic genes that are conserved in hybrid cells and able to perpetuate leukemia in vivo.
authors.affiliation: Laboratory of Hematology-Oncology, European Institute of Oncology, Milan, Italy. ines.martinpadura@ieo.eu
authors.forename: Ines
authors.initials: I
authors.lastname: Martin-Padura
authors.forename: Paola
authors.initials: P
authors.lastname: Marighetti
authors.forename: Giuliana
authors.initials: G
authors.lastname: Gregato
authors.forename: Alice
authors.initials: A
authors.lastname: Agliano
authors.forename: Omar
authors.initials: O
authors.lastname: Malazzi
authors.forename: Patrizia
authors.initials: P
authors.lastname: Mancuso
authors.forename: Giancarlo
authors.initials: G
authors.lastname: Pruneri
authors.forename: Andrea
authors.initials: A
authors.lastname: Viale
authors.forename: Francesco
authors.initials: F
authors.lastname: Bertolini
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology / Q000494:pharmacology; D018952:Antigens, CD34 / Q000378:metabolism; D051928:CD47 Antigen / Q000276:immunology; D045744:Cell Line, Tumor; D002471:Cell Transformation, Neoplastic / Q000235:genetics / Q000378:metabolism; D050676:Core Binding Factor Alpha 2 Subunit / Q000235:genetics / Q000378:metabolism; D003713:Dendritic Cells / Q000378:metabolism; D004195:Disease Models, Animal; D042783:Endothelial Cells / Q000378:metabolism; D005260:Female; D006412:Hematopoietic Stem Cells / Q000378:metabolism; D006801:Humans; D018960:Hyaluronan Receptors / Q000276:immunology; D006822:Hybrid Cells / Q000378:metabolism; D007945:Leukemia, Lymphoid / Q000235:genetics / Q000378:metabolism; D015470:Leukemia, Myeloid, Acute / Q000235:genetics / Q000378:metabolism*; D008264:Macrophages / Q000378:metabolism*; D008297:Male; D008561:Membrane Fusion / Q000187:drug effects; D051379:Mice; D015514:Oncogene Proteins, Fusion / Q000235:genetics / Q000378:metabolism; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000378:metabolism; D000075142:RUNX1 Translocation Partner 1 Protein; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D014183:Transplantation, Heterologous
chemical_list: D000911:Antibodies, Monoclonal; D018952:Antigens, CD34; D051928:CD47 Antigen; D050676:Core Binding Factor Alpha 2 Subunit; D018960:Hyaluronan Receptors; D015514:Oncogene Proteins, Fusion; D011518:Proto-Oncogene Proteins; D000075142:RUNX1 Translocation Partner 1 Protein; C493728:RUNX1 protein, human; C082222:RUNX1T1 protein, human; D014157:Transcription Factors