Susceptibility and resistance to Moloney murine leukemia virus-induced promonocytic leukemia. 1994

V Nazarov, and D Hilbert, and L Wolff
Laboratory of Genetics, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892.

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.

UI MeSH Term Description Entries
D007113 Immunity, Innate The capacity of a normal organism to remain unaffected by microorganisms and their toxins. It results from the presence of naturally occurring ANTI-INFECTIVE AGENTS, constitutional factors such as BODY TEMPERATURE and immediate acting immune cells such as NATURAL KILLER CELLS. Immunity, Native,Immunity, Natural,Immunity, Non-Specific,Resistance, Natural,Innate Immune Response,Innate Immunity,Immune Response, Innate,Immune Responses, Innate,Immunity, Non Specific,Innate Immune Responses,Native Immunity,Natural Immunity,Natural Resistance,Non-Specific Immunity
D007942 Leukemia, Experimental Leukemia induced experimentally in animals by exposure to leukemogenic agents, such as VIRUSES; RADIATION; or by TRANSPLANTATION of leukemic tissues. Experimental Leukemia,Experimental Leukemias,Leukemia Model, Animal,Leukemias, Experimental,Animal Leukemia Model,Animal Leukemia Models,Leukemia Models, Animal
D007948 Leukemia, Monocytic, Acute An acute myeloid leukemia in which 80% or more of the leukemic cells are of monocytic lineage including monoblasts, promonocytes, and MONOCYTES. Leukemia, Monoblastic, Acute,Leukemia, Myeloid, Acute, M5,Leukemia, Myeloid, Schilling-Type,Monoblastic Leukemia, Acute,Monocytic Leukemia, Acute,Myeloid Leukemia, Acute, M5,Myeloid Leukemia, Schilling-Type,Leukemia, Acute Monocytic,Leukemia, Myeloid, Schilling Type,Acute Monoblastic Leukemia,Acute Monoblastic Leukemias,Acute Monocytic Leukemia,Acute Monocytic Leukemias,Leukemia, Schilling-Type Myeloid,Leukemias, Acute Monoblastic,Leukemias, Acute Monocytic,Monoblastic Leukemias, Acute,Monocytic Leukemias, Acute,Myeloid Leukemia, Schilling Type,Schilling-Type Myeloid Leukemia
D008815 Mice, Inbred Strains Genetically identical individuals developed from brother and sister matings which have been carried out for twenty or more generations, or by parent x offspring matings carried out with certain restrictions. All animals within an inbred strain trace back to a common ancestor in the twentieth generation. Inbred Mouse Strains,Inbred Strain of Mice,Inbred Strain of Mouse,Inbred Strains of Mice,Mouse, Inbred Strain,Inbred Mouse Strain,Mouse Inbred Strain,Mouse Inbred Strains,Mouse Strain, Inbred,Mouse Strains, Inbred,Strain, Inbred Mouse,Strains, Inbred Mouse
D008819 Mice, Nude Mutant mice homozygous for the recessive gene "nude" which fail to develop a thymus. They are useful in tumor studies and studies on immune responses. Athymic Mice,Mice, Athymic,Nude Mice,Mouse, Athymic,Mouse, Nude,Athymic Mouse,Nude Mouse
D008969 Molecular Sequence Data Descriptions of specific amino acid, carbohydrate, or nucleotide sequences which have appeared in the published literature and/or are deposited in and maintained by databanks such as GENBANK, European Molecular Biology Laboratory (EMBL), National Biomedical Research Foundation (NBRF), or other sequence repositories. Sequence Data, Molecular,Molecular Sequencing Data,Data, Molecular Sequence,Data, Molecular Sequencing,Sequencing Data, Molecular
D008979 Moloney murine leukemia virus A strain of Murine leukemia virus (LEUKEMIA VIRUS, MURINE) arising during the propagation of S37 mouse sarcoma, and causing lymphoid leukemia in mice. It also infects rats and newborn hamsters. It is apparently transmitted to embryos in utero and to newborns through mother's milk. Moloney Leukemia Virus,Leukemia Virus, Moloney,Virus, Moloney Leukemia
D011519 Proto-Oncogenes Normal cellular genes homologous to viral oncogenes. The products of proto-oncogenes are important regulators of biological processes and appear to be involved in the events that serve to maintain the ordered procession through the cell cycle. Proto-oncogenes have names of the form c-onc. Proto-Oncogene,Proto Oncogene,Proto Oncogenes
D002273 Carcinogens Substances that increase the risk of NEOPLASMS in humans or animals. Both genotoxic chemicals, which affect DNA directly, and nongenotoxic chemicals, which induce neoplasms by other mechanism, are included. Carcinogen,Oncogen,Oncogens,Tumor Initiator,Tumor Initiators,Tumor Promoter,Tumor Promoters,Initiator, Tumor,Initiators, Tumor,Promoter, Tumor,Promoters, Tumor
D004198 Disease Susceptibility A constitution or condition of the body which makes the tissues react in special ways to certain extrinsic stimuli and thus tends to make the individual more than usually susceptible to certain diseases. Diathesis,Susceptibility, Disease,Diatheses,Disease Susceptibilities,Susceptibilities, Disease

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