Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0023418 (leukemia)
 93,477 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

H-2-congeneic C57BL mice with milk transmission of B-tropic murine leukemia virus (V+ mice) have a much higher lymphoma incidence than the same strains without milk-transmitted virus (V- mice). Gene(s) within the major histocompatibility complex (H-2) influence virus titers, lymphoma incidence, lymphoma type and the anti-MuLV envelope antibody response. In this paper, we report that the prevalence of cytotoxic antibodies to virus-induced lymphomas is also regulated by the H-2 complex. Milk transmission of MuLV resulted in the formation of cytotoxic antibodies against primary virus-induced C57BL lymphomas. These antibodies detect an antigen that is also present on the RADAI tumor-cell line, and on normal spleen cells of young adult B10.A (H-2a) mice of both V+ and V- sublines, but not on spleen cells of young adult B10 (H-2a) mice of either subline. These cytotoxic antibodies were detected in the sera of B10V+ and B10.A(5R)V+ animals, but not in the sera of B10.AV+ mice. This indicates that the prevalence of these antibodies is controlled by a gene in the K- and/or I-A region of the H-2 complex. The presence of these cytotoxic antibodies in serum is recessively inherited. The specificity of the cytotoxic antibodies was investigated with a standard panel of transplantable tumor-cell lines. Of these, only the RADAI cells expressed the target antigen in direct cytotoxicity tests and by absorption. The ability of B10V+ sera to lyse the B10.AV+ and RADAI tumor cells is ascribed to antibody activity against a new MuLV-related cell-surface protein: G(B10.A). Immunochemical analysis and absorption experiments with different types of purified MuLV and MuLV-infected cell lines indicate that the cytotoxic antibodies belong to low-avidity IgM antibodies that are directed to MuLV.
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PMID:H-2 control of the cytotoxic antibody response against a newly defined MuLV-related cell-surface antigen: G(B10.A). 630 68

Leukemias induced by neonatal inoculations of several mouse strains with different strains of Friend murine leukemia helper virus (F-MuLV) were followed for time of disease onset, cytochemical analysis of predominant cell types in leukemic organs, and expression of infectious mink cell focus-inducing (MCF) viruses detected by mink cell foci or MCF-specific monoclonal antibodies. Most BALB.B and IRW mice had a rapidly appearing, severe anemia and hepatosplenomegaly consisting of erythroid cells. MCF viruses were usually isolated from enlarged spleens of IRW mice. In contrast, C57BL/10 mice had a lower incidence of disease and much slower course. Splenomegaly and lymphadenopathy with mild anemia were seen, and the predominant cell types were either myeloid (chloroleukemia) or lymphoid. MCF viruses were never isolated from this mouse strain. (C57BL/10 X IRW)F1 mice were intermediate in latency, but all mice had disease by 8 months. Myeloid, lymphoid, and some mixed leukemias with an erythroid component were observed, but in no case did we see the severe anemia or pure erythroid involvement typical of IRW and BALB.B mice. MCF viruses were, however, isolated from 22% of these mice regardless of leukemia cell type. DBA/2 mice had a disease pattern similar to the (C57BL/10 X IRW)F1 mice, and MCF viruses were isolated from three of six mice tested. Inoculation of IRW mice with the low virulence B3 strain of F-MuLV produced disease with a longer latency than F-MuLV 57, but similar cell types were transformed by both viruses. In vitro cell lines were derived from 14 mice, and most were tumorigenic in vivo. Three lines released infectious MCF virus, and three others expressed MCF-specific cell surface antigens but did not release virus. Eight lines expressed no MCF infectious virus or viral antigens. Several lines released infectious xenotropic viruses and/or expressed xenotropic MuLV cell surface antigens recognized by monoclonal antibodies reactive with xenotropic viruses. The lack of MCF expression in many primary leukemic tissues as well as in in vitro derived leukemia cell lines of C57BL/10 and (B10 X IRW)F1 mice suggested that MCF virus generation and expression may not be required for leukemogenesis in some mouse strains or in some hemopoietic lineages.
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PMID:Effect of murine host genotype on MCF virus expression, latency, and leukemia cell type of leukemias induced by Friend murine leukemia helper virus. 630 93

The role of major histocompatibility (MHC) versus non-MHC determinants in the antileukemic effect exerted by engrafted normal marrow (graft-vs-leukemia, GvL) was studied in Rauscher leukemic SJL/J mice. The marrow donor strains included normal syngeneic SJL/J (H-2s), allogeneic C57BL/10 and 129/J (H-2b), congenic B10.S (H-2s, but otherwise genetically identical to the C57BL/10), and also F1 hybrid mice of the SJL/J and B10.S or C57BL/10 strains. Prior to transplant the recipients were exposed to a dose of total body irradiation that was large, but lower than that required to eliminate all hematopoietic precursors, such that GvL activity of the donor marrow would be necessary to avoid leukemic relapse. Total relapse within 60 days was observed when the syngeneic SJL/J donors were used. Transplantation either of the H-2b C57BL/10 or the H-2s B10.S marrow resulted in approximately 50% unrelapsed survival at 4 months. In contrast, only 26% unrelapsed survival was obtained with H-2b 129/J marrow. Marrow from (SJL/J X B10.S)F1 hybrids yielded a survival curve that was intermediate between those for the two parental strains; a similar but somewhat improved pattern was seen with (SJL/J X C57BL/10)F1-hybrid donors. The results suggest that although MHC genetic differences between the donor and recipient may produce a GvL effect in marrow transplantation therapy, other non-MHC determinants may also be capable of exerting an independent GvL effect of at least equivalent strength.
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PMID:Possibility of graft-vs-leukemia determinants independent of the major histocompatibility complex in allogeneic marrow transplantation. 634 Feb 92

Cytolytic T lymphocytes (CTL) specific for the virus-induced and leukemia-associated Friend, Moloney, Rauscher (FMR) antigen are easily detected in the spleens of primary and secondary stimulated H-2b or H-2d mice. They react, respectively, with H-2Db + FMR and H-2Kd + FMR; Dd and Kb never being involved. On the other hand, recombinant (KbDd) mice are relatively low responders that produce CTL only after secondary stimulation. Competition and blocking experiments with monospecific anti-H-2 antibodies have demonstrated that on the same H-2b tumor cells, C57BL/6 (H-2b) lymphocytes recognize Db + FMR, whereas B10.A(5R) lymphocytes recognize Kb + FMR, the restriction cannot, therefore be explained by a specific association of viral molecules with certain H-2 products. The CTL response of (B10 X 5R)F1 hybrids is (a) easily detected in primary reaction, the high responder anti-FMR phenotype being dominant and (b) directed against Db + FMR, F1 mice being low responder against Kb + FMR like the B10 parent. These results suggest that a D region-associated immune response gene controls the cell-mediated anti-FMR reaction, the best available H-2 + FMR antigenic association being chosen by CTL precursors.
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PMID:Immune response genes control T killer cell response against Moloney tumor antigen cytolysis regulating reactions against the best available H-2 + viral antigen association. 677 26

Using a monoclonal antibody raised by fusing spleen cells from A/J mice, immunized with B10.A splenocytes and lymph-node cells, with a BALB/c myeloma, we have described a new surface alloantigen, Ly-21.2, Ly-21.2 is present in varying amounts in all lymphoid tissues, is not detectable in the brain, kidney, lung or erythrocytes, and is found in only trace amounts in the liver. Strain distribution studies showed that Ly-21.2 is present in all strains examined, including B10, except the A strain and segregation analysis of (A/J x B10) F2 mice showed that Ly-21.2 expression (1) is encoded by one gene and (2) is linked to albinism on chromosome 7. Studies performed on mice developing T-cell leukemia showed that, regardless of the etiologic agent, Ly-21.2 expression increases dramatically in mice with overt leukemia. In addition, preliminary studies suggest that expression of Ly-21.2 is linked to increased susceptibility of mice to Friend-virus-induced erythroleukemia.
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PMID:A new murine lymphocyte alloantigen, Ly-21.2, mapping to the seventh chromosome. 680 49

Acute thrombocytopenia and megakaryocyte infection have been investigated during the preleukemic phase of the disease induced by the Rauscher murine leukemia virus (RMuLV) in mice. Injection of RMuLV, either intravenously or intraperitoneally, rapidly induced thrombocytopenia, possibly as a result of direct interaction between platelets and viral particles. The susceptibility to this acute thrombocytopenia was genetically controlled and was inherited as a dominant trait. Murine strains with H-2d or H-2k haplotype, which are susceptible to the induction of leukemia by RMuLV, developed thrombocytopenia, whereas leukemia-resistant H-2b and H-2q strains of mice failed to develop thrombocytopenia. Using B10 H-2-congenic and intra-H-2-recombinant mice, it was shown that the susceptibility to RMuLV-induced thrombocytopenia was controlled by gene(s) in or closely linked to the D region of the H-2 complex. Megakaryocytes may be one of the first sites for the replication of RMuLV. Indeed, among bone marrow cells, only megakaryocytes expressed viral antigens gp70 and p30 during the initial phase of RMuLV infection. In addition, megakaryocytes from infected mice were able to transfer preleukemic thrombocytopenia as well as leukemia in syngeneic mice. The infection of megakaryocytes by RMuLV appears to be genetically controlled in a manner similar to the induction of thrombocytopenia, since only the megakaryocytes from mice developing thrombocytopenia were infected by RMuLV. These results indicate that the gene(s) governing the induction of thrombocytopenia by RMuLV may be the same gene(s) (or closely linked to the gene) that controls the susceptibility to leukemogenesis, and would be consistent with the expression of the gene product, presumably a receptor-like molecule for RMuLV, on platelet and megakaryocyte membranes.
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PMID:Induction of acute thrombocytopenia and infection of megakaryocytes by Rauscher murine leukemia virus reflect the genetic susceptibility to leukemogenesis. 683 48

To isolate a stable tumor cell line source of Interleukin 2 (IL-2 formerly referred to as T cell growth factor), over 40 murine leukemia and lymphoma cells as well as 9 clonal helper and killer IL-2-driven T cell lines were screened for both constitutive and mitogen-stimulated IL-2 production. A radiation-induced splenic lymphoma from the B10.BR mouse, the LBRM-33 cell line, could be stimulated to produce over 1000 units/ml of IL-2 after 24 hr exposure to T cell mitogens. Peak IL-2 activity was found in supernatants harvested from 24-hr cultures of either 1% PHA or 20 micrograms/ml Con A-stimulated LBRM-33 cells (10(6) cells/ml). IL-2 production observed in both serum-free and serum-containing cultures represented between 1000 and 5000 times the quantity of IL-2 produced in conventional cultures of mitogen-activated rat or mouse spleen cells. Peak IL-2 production by LBRM-33 cultures (stimulated at either optimal Con A or PHA concentrations or co-stimulated with suboptimal amounts of mitogen and phorbol myristate acetate) was consistently accompanied by LBRM-33 cell death. Phenotypic characterization of the producer cell revealed LBRM-33 cells to be Thy 1+, Ly 1+, Ly 2+, Ly 3+, Qa 2-3+, Qa 3.2+, Qat 4+, and Ly 5+. These studies provide further evidence that IL-2 is a T cell product and establish a source of IL-2 that will be a valuable reagent for the isolation and further molecular characterization of this immunoregulatory molecule.
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PMID:Biochemical and biologic characterization of lymphocyte regulatory molecules. III. The isolation and phenotypic characterization of Interleukin-2 producing T cell lymphomas. 696 90

A method for infection of lymphocytes with Moloney(Abelson) murine leukemia virus [M(A)-MuLV] is described. Only lymphoblasts obtained after stimulation of normal spleen cells by the B cell mitogen lipopolysaccharide (LPS) were satisfactory targets for virus-specific, secondary cytotoxic T lymphocytes (CTL), whereas spleen cells stimulated by the T cell mitogen concanavalin A were not. The secondary CTL response against M(A)-MuLV could be efficiently measured using M(A)-MulV-infected LPS blasts as stimulating cells for secondary in vitro restimulation and as target cells for virus-specific destruction. Cold target inhibition demonstrated virus specificity of CTL. The T cell character of the cytotoxic cells was demonstrated by their sensitivity to anti-Thy-1.2 treatment. Using syngeneic virus-infected LPS blasts as target and stimulator, CTL responses were measured with effector cells from C57BL mice of the H-2b haplotype and of recombinant haplotypes sharing either K or D alleles with H-2b. In analogy with previous studies on Moloney virus-specific CTL, it was observed that C57BL/6 (H-2b) effector cells predominantly lysed Db-compatible, virus-infected target cells; B10.A(5R), (KbDd) effector cells showed a poor CTL response against syngeneic, virus-infected target cells. The combined findings indicate the existence of an Ir gene in the H-2D region regulating the CTL response against Moloney leukemia virus.
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PMID:Cytotoxic T cell response against lymphoblasts infected with Moloney (Abelson) murine leukemia virus. Methodological aspects and H-2 requirements. 697 10

The incidence of leukemias was established in mice of different inbred strains inoculated with Moloney leukemia virus (M-MuLV), and a complex genetic control was found. To characterize the different steps of the host-virus relationship further, the degree of viremia, the appearance of leukemia, organ involvement, and the surface phenotype of leukemic cells were studied in individual mice. The results demonstrate that: a) The viremia was controlled by H-2 and non-H-2 genes. Three H-2 genes located in the I and D or T region of the MHC behave like immune-response genes controlling the specific antiviral immune response. Other gene(s) mapped outside the complex also affected the virus production. Both sets of genes influenced leukemia incidence, since leukemias were observed only in highly viremic strains. b) Additional non-H-2 genes, which were not involved in viremia control, were determinants in the induction of malignancies because some sensitive strains do not become leukemic despite high levels of viremia. c) The anatomical type of Moloney virus-induced leukemias varied according to the non-H-2 background. Most of the leukemias arising in B10 congeneic mice involved the thymus and were frequently limited to this organ, whereas BALB mice preferentially developed splenic leukemias. d) In a given inbred strain, the leukemias arising in different animals frequently expressed different phenotypes. It can be concluded that Moloney virus-induced leukemia is a multistep process, viral production being necessary but not sufficient in and of itself to induce a malignant transformation.
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PMID:Incidence and phenotypic heterogeneity of Moloney virus-induced leukemias: a multigenic control. 697 41

Previous studies showed that treatment of mice with 5(3,3'-dimethyl-1-triazeno)-amidazole-4-carboxamide (DTIC) plus cyclophosphamide (Cy) produce profound depression of classical allograft responses and impairment of endogenous cell proliferation similar to that detectable in lethally-irradiated mice. However efficient localized graft resistance was found in the spleen of drug-treated hybrid or allogeneic mice challenged with lymphoma cells. The present report describes the genetic patterns of this type of natural resistance [hereafter called drug-resistant inhibition of tumors (DRIT) in various tumor-host combinations DRIT was evaluated measuring the extent of 125I-5-iodo-2'-deoxyuridine (125IUdR) uptake in the spleen and liver of leukemic hosts. The results of the experiments performed with two H-2d (i.e. L1210 and LSTRA), one H-2b (i.e. L5MF-22) and one H-2a (i.e. LAF-17) lymphomas inoculated into drug-treated recipients pointed out that: (a) tumor cell proliferation was markedly inhibited in the spleen and weakly or not impaired in the liver of D end Hh-1-incompatible euthymic or nude mice responder for the hh system; (b) no resistance was found in the spleen and liver of Hh-1-compatible B10.A (2R) mice against L5MF-22 lymphoma or of SJL recipients genetically non-responder for the Hh system, against LSTRA cells; (c) splenic resistance against L1210 leukemia was detectable in Hh-compatible B10.A or B10.A (5R) mice; (d) splenic and liver resistance was found in Hh-incompatible but genetically Hh non-responder SJL or C3H mice against L5MF-22 or LSTRA lymphomas, respectively. These results showed that the genetic patterns of the DRIT system parallels the Hh-type immunity in certain tumor-host combinations [(a) and (b)] but not in others [(a) and (d)], as previously detected in lethally-irradiated mice. It is concluded that genetically-controlled lymphoma graft resistance can be retained by mice treated with high doses of antitumor drugs, capable of abrogating classical T-dependent transplantation immunity.
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PMID:Transplantation resistance of drug-treated allogeneic mice against murine lymphomas--II. Studies with various tumor-host combinations. 733 20


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