EWS/FLI-1 induces rapid onset of myeloid/erythroid leukemia in mice.

Torchia EC, Boyd K, Rehg JE, Qu C, Baker SJ
Mol Cell Biol. 2007 27 (22): 7918-34

PMID: 17875932 · PMCID: PMC2169157 · DOI:10.1128/MCB.00099-07

EWS/FLI-1 is a chimeric oncogene generated by chromosomal translocation in Ewing tumors, a family of poorly differentiated pediatric tumors arising predominantly in bone but also in soft tissue. The fusion gene combines sequences encoding a strong transactivating domain from the EWS protein with the DNA binding domain of FLI-1, an ETS transcription factor. A related fusion, TLS/ERG, has been found in myeloid leukemia. To determine EWS/FLI-1 function in vivo, we engineered mice with Cre-inducible expression of EWS/FLI-1 from the ubiquitous Rosa26 locus. When crossed with Mx1-cre mice, Cre-mediated activation of EWS/FLI-1 resulted in the rapid development of myeloid/erythroid leukemia characterized by expansion of primitive mononuclear cells causing hepatomegaly, splenomegaly, severe anemia, and death. The disease could be transplanted serially into naïve recipients. Gene expression profiles of primary and transplanted animals were highly similar, suggesting that activation of EWS/FLI-1 was the primary event leading to disease in this model. The Cre-inducible EWS/FLI-1 mouse provides a novel model system to study the contribution of this oncogene to malignant disease in vivo.

MeSH Terms (21)

Animals Cell Line Cell Proliferation Chimera Chromosome Aberrations GATA1 Transcription Factor Gene Expression Profiling Leukemia, Myeloid Mice Mice, Inbred C57BL Mice, Inbred NOD Mice, SCID Mice, Transgenic Neoplasm Transplantation Oncogene Proteins, Fusion Proteins Proto-Oncogene Protein c-fli-1 RNA, Untranslated RNA-Binding Protein EWS Sarcoma, Ewing Stem Cells

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