10A1 MuLV induces a murine leukemia that expresses hematopoietic stem cell markers by a mechanism that includes fli-1 integration.
The 10A1 murine leukemia virus induces tumors that lack lineage-specific markers found on myeloid, T-cell, and B-cell lineages. Either erythroid or multipotent stem cells can have this phenotype; therefore we have used fluorescence-activated cell sorter analysis with either multipotent stem cell markers or markers found on lineage-restricted precursors to differentiate between these two possibilities. The results showed that tumors induced by 10A1 expressed multipotent stem cell markers as well as some lineage-restricted precursor markers. To further study the tumor phenotype, we analyzed total RNAs from 10A1-induced tumors by Northern blotting for c-kit, erythropoietin receptor, and T-cell gamma receptor mRNAs. Most of the tumors contained these mRNAs, which are characteristic of early hematopoietic cells. These results are consistent with the hypothesis that 10A1-induced tumor cells are early multipotent hematopoietic stem cells. Southern blot analysis revealed that 14 of 14 10A1-induced tumor cell DNAs examined contained MuLV integrations into the fli-1 gene. The results strongly suggested that promoter insertion into fli-1 is required for tumor formation.
Laboratory of Molecular Virology and Carcinogenesis, PRI/DynCorp, Inc., NCI-Frederick Cancer Research and Development Center, Maryland 21702-1201.
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Ott
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Keller
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D000818:Animals; D000943:Antigens, Differentiation / Q000097:blood*; D001483:Base Sequence; D002469:Cell Separation; D004268:DNA-Binding Proteins / Q000235:genetics*; D005434:Flow Cytometry; D006412:Hematopoietic Stem Cells / Q000737:chemistry* / Q000473:pathology; D009052:Leukemia Virus, Murine / Q000235:genetics / Q000502:physiology*; D007942:Leukemia, Experimental / Q000097:blood* / Q000235:genetics / Q000821:virology; D051379:Mice; D008969:Molecular Sequence Data; D051789:Proto-Oncogene Protein c-fli-1; D011518:Proto-Oncogene Proteins; D011519:Proto-Oncogenes / Q000235:genetics; D012192:Retroviridae Infections / Q000097:blood / Q000235:genetics; D015534:Trans-Activators / Q000235:genetics*; D014412:Tumor Virus Infections / Q000097:blood / Q000235:genetics; D016662:Virus Integration / Q000235:genetics*
D000943:Antigens, Differentiation; D004268:DNA-Binding Proteins; C497426:Fli1 protein, mouse; D051789:Proto-Oncogene Protein c-fli-1; D011518:Proto-Oncogene Proteins; D015534:Trans-Activators