TY - JOUR
T1 - Spontaneous cell fusion of acute leukemia cells and macrophages observed in cells with leukemic potential
AU - Martin-Padura, Ines
AU - Marighetti, Paola
AU - Gregato, Giuliana
AU - Agliano, Alice
AU - Malazzi, Omar
AU - Mancuso, Patrizia
AU - Pruneri, Giancarlo
AU - Viale, Andrea
AU - Bertolini, Francesco
N1 - Funding Information:
Abbreviations: AML, acute myeloid leukemia; ALL, acute lymphoblastic leukemia; NS, NOD/LtSz-Prkdcscid; NSB, NOD.Cg-PrkdcscidB2mtm1Unc; NSG, NOD.cg-PrkdcscidIl2rgtm1Wjll; MFR, macrophage fusion receptor; BM, bone marrow; PB, peripheral blood; FISH, fluorescence in situ hybridization; ip, intraperitoneally; iv, intravenously; IL, interleukin Address all correspondence to: Ines Martin-Padura, PhD, Laboratory of Hematology-Oncology, European Institute of Oncology, Via Ripamonti 435, 2041 Milan, Italy. E-mail: ines.martinpadura@ieo.eu 1This investigation was supported in part by Associazione Italiana per la Ricerca sul Cancro (AIRC), Istituto Superiore di Sanita (ISS), Italian Ministry of Health, and Fondazione Umberto Veronesi. 2This article refers to supplementary materials, which are designated by Table W1 and Figures W1 to W9 and are available online at www.neoplasia.com. Received 27 April 2012; Revised 15 September 2012; Accepted 19 September 2012 Copyright © 2012 Neoplasia Press, Inc. All rights reserved 1522-8002/12/$25.00 DOI 10.1593/neo.12736
PY - 2012/11
Y1 - 2012/11
N2 - 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.
AB - 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.
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U2 - 10.1593/neo.12736
DO - 10.1593/neo.12736
M3 - Article
C2 - 23226099
AN - SCOPUS:84869187934
SN - 1522-8002
VL - 14
SP - 1057
EP - 1066
JO - Neoplasia (United States)
JF - Neoplasia (United States)
IS - 11
ER -