Susceptibility and resistance to Moloney murine leukemia virus-induced promonocytic leukemia.
Moloney murine leukemia virus (M-MuLV) induces promonocytic leukemias, called MML, in pristane-treated adult mice. These tumors invariably express fused gag-myb mRNA as a consequence of virus integration and activation of the c-myb locus. In the present study it was determined that while BALB/c and DBA/2N mice are highly susceptible, C57BL/6, C3H/He, STS/A, NFS, NIH/Swiss, SJL/J, and NZB mice are strongly resistant to tumor induction. Although C57BL/6 mice were resistant because they were unable to support early virus replication in hematopoietic tissue, NFS and C3H/He mice supported replication and were shown, using RT-PCR, to have cells in the bone marrow and spleen that expressed the aberrant, leukemia-related gag-myb mRNA. This provided evidence that early stages of leukemia were permitted to develop in these mice, but preneoplastic cells were unable to progress to the acute phase. Experiments in which MML was induced by M-MuLV plus pristane treatment in immunodeficient C3H/He nu/nu and sublethally irradiated C3H/He mice suggested that the immune response may play a role in eliminating preleukemic cells in immunocompetent C3H/He. Tumors from these mice had rearrangements at the c-myb locus and expressed gag-myb RNA. It was concluded that, at least in the case of C3H/He mice, resistance is not due to an inability of virus to activate c-myb or to a lack of other tumor promoting events. Rather, leukemia development appears to be restricted by an immune response, presumably T-cell mediated. Evidence is provided that non-H-2 MHC genes are required for resistance in both C57BL/6 and C3H/He mice and that resistance is dominant. This provides an animal model for the study of tumor progression as it relates to the immune response.
Laboratory of Genetics, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892.
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Nazarov
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Hilbert
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Wolff
D016475:3T3 Cells; D000818:Animals; D001483:Base Sequence; D002273:Carcinogens; D004198:Disease Susceptibility / Q000276:immunology; D005260:Female; D020022:Genetic Predisposition to Disease; D006183:H-2 Antigens / Q000235:genetics; D007113:Immunity, Innate / Q000235:genetics / Q000276:immunology; D007942:Leukemia, Experimental / Q000235:genetics / Q000276:immunology / Q000503:physiopathology* / Q000821:virology; D007948:Leukemia, Monocytic, Acute / Q000821:virology; D051379:Mice; D008815:Mice, Inbred Strains; D008819:Mice, Nude; D008969:Molecular Sequence Data; D008979:Moloney murine leukemia virus / Q000276:immunology / Q000472:pathogenicity*; D011519:Proto-Oncogenes; D012192:Retroviridae Infections / Q000235:genetics / Q000276:immunology / Q000503:physiopathology*; D013045:Species Specificity; D013729:Terpenes; D014412:Tumor Virus Infections / Q000235:genetics / Q000276:immunology / Q000503:physiopathology*; D014779:Virus Replication; D014916:Whole-Body Irradiation
D002273:Carcinogens; D006183:H-2 Antigens; D013729:Terpenes; C009042:pristane