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Query: UMLS:C0023418 (leukemia)
 93,477 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Leukemia was observed in 45 per cent of hairless mice at 8 to 10 months of age and 72 per cent at 18 months. The incidence of leukemia in normal heterozygous mice of the same age is about one per cent at 10 months and increases to 20 per cent at 18 months. Other tumors are rare; two mammary adenocarcinomas occurred in heterozygotes, and an epidermal squamous cell carcinoma was found in a hairless mouse. Murine leukemia virus was isolated from normal and leukemic mice of both genotypes on SWR/J- and C57L/J-METC, but not BALB/cJ-METC. If this virus is responsible for the leukemia in HRS/J mice, the mutant gene (hr) enhances susceptibility and the wild-type allele (+) induces resistance to leukemogenesis, i.e., malignant transformation of reticulo-endothelial tissues occurs rather than inhibition of viral replication as both genotypes harbor virus in high titers. The two types of HRS/J mice, hr/hr and hr/+, are congenic, i.e., they differ only with respect to one allele (hr or +) at the mutant locus. This single gene difference should lend itself to analysis of the interaction of a specific gene and murine leukemia virus.
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PMID:Genetic control by the hr-locus of susceptibility and resistance to leukemia. 431 May 15

Spontaneous thymic leukaemia in experimental mice is the result of a complex series of genetically controlled events. An important step in this process involves the production by thymocytes of recombinant polytropic retroviruses (MCF viruses). These leukaemogenic agents arise by recombination of genes from the env regions of endogenous precursor viruses. Sequences in these regions encode the envelope glycoprotein gp70 (ref. 6). Thus far, each cloned isolate of recombinant virus from AKR and HRS/J mice has been found to possess unique oligonucleotide sequences in its env region, as well as clone-specific peptides in its gp70 (refs 7,8). Therefore, the polytropic viruses of these leukaemia-susceptible mice are extremely diverse. These findings suggest that random recombination of env genes gives rise to leukaemogenic polytropic viruses. McGrath and Weissman have proposed that thymocytes with cell surface receptors for the gp70 of a particular leukaemogenic virus are the target cells for malignant transformation by that specific virus. In view of the diversity of polytropic viral gp70, their hypothesis would predict extensive phenotypic diversity among spontaneous thymic leukaemias. In contrast, leukaemias induced by a particular leukaemogenic recombinant virus would always have the same phenotype. Here we verify these predictions experimentally.
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PMID:Surface phenotypes in T-cell leukaemia are determined by oncogenic retroviruses. 625 35

HRS/J, hr/hr and hr/+ mice were evaluated for their ability to resist challenge with a syngeneic tumor, HTU, and for their ability to mount a protective immune response when immunized in vivo with inactivated HTU cells previous to challenge with viable tumors. The heterozygous (hr/+) mice responded more strongly than the homozygous (hr/hr) mice. This response was characterized by the presence of an enhanced ability of spleen cells from immunized mice to form blasts in vitro when incubated with purified murine leukemia viruses (MuLV). We conclude that the in vivo response of HRS/J mice against this tumor is directed, in part, against MuLV antigens expressed on the tumor cells and that the relatively weak response of hr/hr spleen cells to these antigens may be mechanistically linked to their tumor susceptibility.
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PMID:Immune responsiveness of HRS/J mice to syngeneic lymphoma cells. 626 51

Hairless (hr/hr) mice segregating for SJL/J and HRS/J genes (SJL-HRS) were compared to their haired counterparts with respect to immune responsiveness, tumour development and ecotropic murine leukemia virus (MuLV) expression. Homozygosity at the hairless locus did not affect expression of MuLV. There was however, a significant depression of the cellular immune response of these mice as characterized by depressed reactions in phytohemagglutinin, concanavalin A and mixed leukocyte assays. Haired and hairless mice did not differ significantly in response to B-cell mitogens or in production of cytotoxic antibody. The depressed cellular immune response in hr/hr mice is associated with a distinctive histologic type of spontaneous reticulum cell sarcomas. The importance of these results in relation to previous studies of HRS/J hairless mice is discussed.
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PMID:Immunodeficiency and reticulum cell sarcoma in mice segregating for HRS/J and SJL/J genes. 629 51

A recombinant DNA clone, named AL10, that contains murine leukemia virus (MuLV) related sequences was isolated from BALB/c mouse chromosomal DNA and examined in detail. Restriction endonuclease mapping revealed that the 10.5 kbp EcoRI insert consists of a 3.6 kbp left flanking cellular DNA region and a 6.9 kbp MuLV-related region that has a typical proviral LTR-gag-pol-env structure up to the EcoRI site in the env gene region. Comparison of the AL10 map with ecotropic and xenotropic virus isolates revealed many common restriction sites in the LTR and pol gene regions, but much fewer in the leader and gag regions. A stretch of 1,700 nucleotides containing the cellprovirus junctional region was sequenced and revealed transcriptional consensus signals and other structural features characteristic of MuLV LTRs, as well as two distinctive features: (a) a sequence of approximately 170 bp with direct and inverted terminal repeats not seen in infectious MuLV LTRs was identified in the U3 region between the "enhancer" region and the "CAT" box. This novel segment or its homologous sequences appear to be present in most of the endogenous MuLV-related LTRs and in other chromosomal locations of the mouse (b) The tRNA primer binding site is not complementary to proline tRNA, the primer for all known MuLVs, but is a 17/18 match with rat glutamine tRNA. The integration site of AL10 provirus was in a unique DNA region but contained an "Alu"-like short interdispersed repeat in the 5' adjacent cellular region. The AL10 proviral integration found in BALB/c was also apparent in RFM, AKR and SENCAR mouse cells but not in cells of NFS/N, C3H, HRS/J, SC-1, and a California Lake Casitas wild mouse.
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PMID:A novel sequence segment and other nucleotide structural features in the long terminal repeat of a BALB/c mouse genomic leukemia virus-related DNA clone. 631 May 6

The biological and genetic characteristics of murine leukemia viruses (MuLV) derived from leukemic and normal HRS/J mice were studied. T1-oligonucleotide fingerprinting and mapping of viral RNAs from unpassaged isolates revealed the presence of complex mixtures of viral genomes. MuLV that were purified by endpoint dilution were genetically heterogeneous. Thus, endogenous retroviral sequences expressed in the tissues of HRS/J mice readily recombined with one another. Furthermore, the regular recovery of recombinant ecotropic MuLV suggested reciprocal in vivo complementation of a genetic defect(s) in each of the endogenous ecotropic proviruses Emv-1 and Emv-3. Some recombinant ecotropic viruses contained sequences in the p15E-U3 region that were not derived from Emv-1 and Emv-3 but were found in recombinant polytropic HRS/J viruses. Finally, comparison of the genetic structures of leukemogenic and nonleukemogenic MuLV of this strain implied that the oncogenic phenotype of these MuLV is encoded within env or the U3 region of the genome or both. Our results are consistent with a stepwise convergent evolution of recombinant MuLV in vivo in individual HRS/J mice. Ultimately, this process of selection results in formation of leukemogenic polytropic viruses.
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PMID:Role of recombinant ecotropic and polytropic viruses in the development of spontaneous thymic lymphomas in HRS/J mice. 632 40

An immunologic analysis of mutants HRS/J mice was done comparing hr/hr homozygotes to hr/+ heterozygotes. It was shown that hr/hr spleen but not lymph node cells show a defect specific for functions associated with T helper cells as compared to hr/+ littermates. This defect, which is expressed by depressed proliferative responses to alloantigens, does not affect the ability of hr/hr spleen cells to respond normally to T cell mitogens nor does it affect their ability to generate normal cytotoxic effector cells in vitro. It is further suggested that this defect is due to an abnormality in thymus epithelium, which is also related to the high grade expression of xenotropic virus in old hr/hr thymocytes and subsequent development of leukemia.
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PMID:Immunologic abnormalities in HRS/J mice. I. Specific deficit in T lymphocyte helper function in a mutant mouse. 644 27

The murine leukemic strain HRS/J has an autosomal-recessive, mutant gene, hr, with homozygotes (hr/hr) having a 72% incidence of thymic leukemia at 18 months of age compared to 20% in heterozygotes (hr/+). This study was done to (a) determine if expression of thymocyte differentiation and murine leukemia virus (MuLV) antigens during leukemic transformation were different in hr/hr compared to hr/+ mice, (b) define the subpopulations that were targets for leukemic transformation, and (c) compare the results to reports in other leukemic strains. Flow cytometry analysis of thymus cell suspensions was done with anti-T-cell and anti-H-2 monoclonal antibodies, peanut agglutinin (PNA), and heteroantisera to MuLV antigens. Thymocytes of 1- to 3-month-old HRS/J mice were Thy 1.2+, Lyt 1+2+, H-2Kk-, and MuLV- with an immature-nonactivated phenotype, i.e., PNA+, and Iak-. Preleukemic and leukemic thymocytes showed diversity in expression of Thy 1.2 and Ly antigens with increased H-2Kk and MuLV expression. No differences in phenotype patterns were noted between hr/+ and hr/hr mice during the time course of leukemogenesis. Persistently high PNA/low Iak expression of preleukemic and leukemic thymocytes indicated that the target for HRS leukemic transformation was an immature-nonactivated thymocyte subpopulation in contrast to AKR/J mice in which leukemic transformation involves a mature-activated thymocyte subpopulation. These findings suggest that spontaneously generated leukemogenic viruses in HRS mice have tropism for thymocytes of an immature-nonactivated phenotype.
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PMID:Leukemic transformation in hrs mice occurs in an immature-nonactivated thymocyte subpopulation. 669 74

The production of recombinant retroviruses is an important episode in the natural history of thymic leukaemia in AKR and HRS/J (hr/hr) mices. These viruses apparently originate from ecotropic and xenotropic precursors in the late preleukaemic stage of the disease. Analyses of their structural proteins and genomic oligonucleotides indicate that they arise by recombination of env genes of the precursor viruses. This event leads to a viral envelope glycoprotein (gp70) with some peptides that have features of the gp70 glycoproteins of ecotropic and xenotropic viruses, and others that are unique for each recombinant virus. The former property explains the broad host range of recombinant viruses, and hence their designation as dual tropic or polytropic viruses. It has been postulated that the unique aspect of each recombinant's gp70 determines the phenotypes of leukaemic cells. Polytropic viruses may be highly thymotropic. Their systemic administration results in an infection that confines itself virtually to the thymus. Moreover, these viruses are leukaemogenic whereas their precursors are not, or only weakly so. The leukaemogenicity of polytropic viruses is, however, restricted to certain inbred strains of mice. The HRS/J isolate PTV-1 is leukaemogenic in HRS/J and CBA/J mice, but not in SWR/J or NIH/Swiss mice. The experiments described here demonstrate that a single dominant gene permits infection by thymocytes by a leukaemogenic polytrophic virus. CBA/J mice, which develop thymic leukaemia after infection by this virus, posesses this gene, whereas leukaemia-resistant NFS mice lack it.
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PMID:A single dominant gene determines susceptibility to a leukaemogenic recombinant retrovirus. 725 16

HRS/J inbred mice carry a mutant autosomal recessive gene (hr), which in homozygotes coincides with susceptibility to spontaneous thymic leukemia. Unlike their heterozygote (hr/+) littermates, hr/hr homozygotes express high levels of xenotropic virus during the preleukemic period, and viruses with a broadened host range (termed polytropic viruses) can be isolated from their preleukemic and leukemic tissues. Because hr/hr and hr/+ mice are otherwise genetically identical, the virological differences between them support the role of polytropic viruses in the generation of thymic leukemia. In the present report we show that the HRS/J polytropic viruses are env gene recombinants with unique oligonucleotide and peptide maps. These polytropic viruses appear to arise by recombination between ecotropic virus and an unidentified genome related, but not identical to, the endogenous xenotropic viruses. Moreover, polytropic viruses not only accelerate leukemogenesis in HRS/J mice, but also induce thymic leukemia in the low leukemia strain CBA/J. By contrast, cloned ecotropic and xenotropic viruses have no leukemogenic action.
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PMID:Expression of leukemogenic recombinant viruses associated with a recessive gene in HRS/J mice. 740 Jul 58


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