Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0598766 (leukemogenesis)
 4,065 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A morphologically flat revertant of mink cells nonproductively infected with Moloney sarcoma virus exhibited contact inhibition and lacked detectable sarcoma virus RNA. Superinfection by usually nontransforming type C mammalian leukemia-causing viruses induced transformation and increased sarcoma virus RNA. The results suggest a model for leukemogenesis in animals by increasing, during replication of usually nontransforming leukemia viruses, the levels of RNA from potentially oncogenic cell or integrated virus transforming genes.
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PMID:Increased sarcoma virus RNA in cells transformed by leukemia viruses: model for leukemogenesis. 17 44

AKR/J mice, 80-90% of which ordinarily die of spontaneous lymphocytic leukemias by 12 months of age, were significantly protected from developing leukemia in the initial experiment by a single course of treatment with AKR serotype-specific antibodies mad in goats and processed as immune gamma globulin (IgG). In experiment 1, IgG was given on the day of birth and on four additional days, and finished on day 14. This schedule resulted in suppression of over 4 logarithms of normal virogene expressions up to 25 days of age and led to partial viral suppression for over 200 days of age. At 365 days of age, 20 of 24 (83.3%) control animals were dead of leukemia whereas six of 30 (20%) treated animals had died of leukemia. In a second experiment, only four inoculations of IgG were given from birth to 20 days, after which they were given three inoculations of radiation-killed vaccine specific for AKR-Gross leukemia virus and one injection of murine sarcoma virus-Gross leukemia virus 10 days later. This combined immunization procedure provided significant virus suppression up to 288 days of age. At 300 days of age, 30 of the 50 (60%) controls had died of leukemia while only 1 of 24 (4.2%) of the immunized mice developed fatal leukemia; the significance of protection for each of the experiments was P LESS THAN 0.001. We conclude that these data establish in classical fashion with type-specific immunosuppression the determining role of type-C endogenous virogenes in leukemogenesis and, at the same time, also established the feasibility of nearly total prevention of leukemia in AKR mice.
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PMID:Prevention of spontaneous leukemia in AKR mice by type-specific immunosuppression of endogenous ecotropic virogenes. 18 47

The purpose of this study was to develop an animal system of protective immunity against oncornaviruses and to test whether such immunization had an inhibitory effect upon chemical sarcomagenesis. Several murine sarcoma virus (MSV) pseudotypes were used as immunogens and tested against themselves, against other pseudotypes, against leukemogenesis by their helper viruses, and against sarcomagenesis by 3-methylcholanthrene. Five MSV pseudotypes were obtained by rescuing complete MSV from MSV-genome carrier, nonproducer hamster tumor cells, using five different leukemia viruses as helpers. The immunogenic properties of these pseudotypes could be specified on the basis of the following observations. 1) They all induced sarcomas in newborn mice and regressing sarcoma nodules in young adult mice. After regression, most mice remained free of neoplastic disease, but some developed sarcoma or leukemia relapses. 2) They had an individual host range pattern, usually determined by the helper virus, as tested by inoculation of a constant virus dose in BALB/c, C57BL/Ka, and Swiss mice. 3) They were all immunogenic, in the sense that the first virus inoculation prevented sarcoma induction by a second challenge, either viral or cellular. 4) They were cross-reactive in vivo, one pseudotype immunizing against another, in the combinations tested. 5) They were able to immunize against leukemogenesis induced by their helper viruses. This was shown by prevention of leukemic deaths by Rauscher and Friend viruses, by a slight prolongation of survival after challenge with the Precerutti-Law leukemia virus, and by inhibition of splenomegaly by Moloney leukemia virus. In a second stage of the study, we investigated whether immunization with any of the MSV psuedotypes had an inhibitory effect upon sarcomagenesis induced by near-threshold doses of 3-methylcholanthrene. The incidence of these sarcomas was essentially the same in virus-immunized and control mice. It was concluded that immunizing procedures able to prevent sarcomagenesis when the inducer is a virus did not have any consistent preventive effect when the inducer was a chemical.
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PMID:Murine sarcoma virus pseudotypes used as immunogens against viral and chemical oncogenesis. 19 61

Prolonged replication of pluripotential stem cells and committed progenitor cells is sustained for prolonged periods in a murine marrow culture system. Alterations in stem cell replication and differentiation are observed after infection of the cultures with Friend virus and Kirsten sarcoma virus consistent with transformation of pluripotential stem cells in the first case and transformation of the macrophage component of the hemopoietic microenvironment in the second. Prolonged myelopoiesis and CFU-c proliferation was also observed in continuous human and prosimian marrow cultures, suggesting the applicability of this technique for analysis of stem cell control and in vitro leukemogenesis in species other than the mouse.
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PMID:Pluripotential stem cell replication in continuous human, prosimian, and murine bone marrow culture. 55 91

Growth of tumors was inhibited or enhanced in mice by a synthetic (pyran) or a biologic (corynebacterium parvum) immunopotentiator. Marked inhibition of leukemogenesis induced by Friend leukemia virus was produced by prophylactic intraperitoneal treatment with pyran, while intravenous treatment with pyran (in the same dose and regimen) significantly enhanced growth of tumor virus. Paradoxical effects were also seen with the biologic immunopotentiator C. parvum in solid tumor systems. Treatment with C. parvum either potentiated disease or had no effect on the life span of most mice bearing the Lewis lung carcinoma. In contrast, the same treatment could produce a high percentage of tumor regressions in mice bearing the MCA 2182 sarcoma, although the effect was somewhat variable. These data, which show that a change in route of drug administration or in the type of tumor treated may reverse the effect of treatment, emphasize that the mechanism of action of immunopotentiators must be elucidated before consistent beneficial treatment of tumor viruses or tumors can be achieved.
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PMID:Paradoxical effects of immunopotentiators on tumors and tumor viruses. 93 3

32D C13(G) is an interleukin 3(IL3)-dependent non-tumorigenic murine hematopoietic cell line which undergoes terminal differentiation into granulocytes when exposed to granulocytic colony stimulating factor (G-CSF). Infections of 32D C13(G) cells with either Kirsten rat sarcoma virus or Balb murine sarcoma virus, both containing a v-ras oncogene, generates clones that can permanently grow in G-CSF without differentiation. 32D-Ki-ras cells show a heterogeneous morphology ranging from the promyelocytic to the myelocytic stage of differentiation, and express high levels of both myeloperoxidase (MPO) and lactoferrin (LF) mRNA. 32D-Ha-ras cells show a more immature phenotype and express MPO but no LF mRNA. The apparent differentiation block of both 32D Ki-ras and 32D Ha ras can be reversed by treatment with the chemical inducers retinoic acid, sodium butyrate or dimethylsulphoxide, which leads to terminal differentiation into granulocytes. When 32D-Ki-ras and 32D-Ha-ras cells are cultured in medium containing IL-3 they become adherent and express some monocyte-macrophage markers. Upon prolonged exposure to IL3, 32D-Ki-ras, but not 32D-Ha-ras, resume suspension growth. Both 32D-Ki-ras and 32D-Ha-ras rapidly die if grown in chemically defined medium in the absence of any growth factor and are non-tumorigenic in immunosuppressed mice. These findings indicate that ras activation may interfere with the normal response to growth and differentiation factors in cells of the granulocytic lineage. These alterations may represent a critical, although non-sufficient, step in leukemogenesis.
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PMID:Alteration of growth and differentiation factors response by Kirsten and Harvey sarcoma viruses in the IL-3-dependent murine hematopoietic cell line 32D C13(G). 246 24

The hematopoietic disregulation in adult mice induced by the malignant histiocytosis sarcoma virus (MHSV) and the Harvey murine sarcoma virus (Ha-MuSV), which both possess c-Ha-ras-related oncogenic sequences, was investigated. Spleen focus formation induced by MHSV and Ha-MuSV was not restricted by the Fv-2 resistance locus in congenic DDD and C57BL/6 mice, unlike leukemogenesis induced by Friend virus, Rauscher virus, and the myeloproliferative sarcoma virus (MPSV). C57BL/6 mice were much more resistant to MHSV and Ha-MuSV-induced spleen focus formation than DDD mice regardless of their Fv-2 state. Infection of DDD mice with MHSV caused a systemic histiocytic neoplasia, best described as murine malignant histiocytosis. Transformed histiocytic cells proliferated excessively in the bone marrow, spleen, and lymph nodes and, in the final stages of the disease, in all major parenchymal organs. The Ha-MuSV caused a strikingly different benign histiocytic tumor in DDD mice and, unlike MHSV, did not induce a rapid, progressive splenomegaly in C57BL/6 mice. Infection of DDD mice with MHSV induced a rapid and synchronized depletion of early and late erythroid precursor cell pools. In MHSV-infected C57BL/6 mice comparable changes were observed with dissimilar kinetics. Macrophage colony-forming cells of MHSV-infected mice were increased in number and proliferated independently of stimulating growth factors. The disease induced by MHSV in mice can thus serve as a model for malignant histiocytosis in humans.
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PMID:Murine retrovirus-induced malignant histiocytosis, an experimental model for the disease in humans. 282 12

How and where erythropoiesis is maintained during advanced leukemic disease is an important and, as yet, unresolved question in hematology. To address the potential role of T-lymphocytes as cells that regulate CFU-E differentiation during leukemogenesis, an experimental model of disease has been developed in inbred Balb/c mice. Specifically, three-week-old Balb/c By mice were injected with murine sarcoma virus-murine leukemia virus-Moloney (MSV-MuLV-M), which resulted 6-8 months later in the development of immunoblastic T-cell sarcomas with a leukemic phase. Splenic T cells from either normal or tumor-bearing mice were assessed for their relative ability to modulate erythroid differentiation. Quantitatively, T cells, Ly1 or Ly 2,3 T-cell subsets isolated from tumor-bearing animals significantly enhanced erythropoiesis when compared with comparable normal T-cell subsets. These data suggest that the compensatory shift of erythropoiesis from the bone marrow to the spleen observed during leukemogenesis was facilitated by splenic T cells. In this circumstance, the enhanced erythropoietic function may be mediated by splenic T cells, which are selectively activated by virus.
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PMID:T-cell regulation of erythropoiesis during acute lymphoblastic leukemia. 387 5

We analyzed the relationship of genetic factors determining the expression of endogenous type-C RNA tumor viruses and other host-gene markers to tumorigenesis. A hybridization experiment was performed with mice of strains AKR/J and C57L, the first filial (F(1)) generation hybrids, the second filial (F(2)) generation hybrids, and the backcrosses to the two parental strains. The results demonstrated a highly significant and predictable association between the expression of complete infectious virus or the viral group-specific (gs) antigen in spleens of young mice and tumorigenesis later in life. Most of the tumors were thymic leukemia and reticulum sarcoma, but other mesenchymal, as well as epithelial, tumors were also observed. Tumors occurred preferentially in gs-antigen- or virus-positive mice of all crosses; in the C57L-backcross and F(2) mice segregating for gs-antigen and virus expression, a few gs-antigen-negative mice developed reticulum cell sarcomas. At the time of their occurrence, the mice were all gs-antigen-positive, and most had virus as well.A minor effect of the major histocompatibility locus, H-2, on leukemogenesis was found in the F(2) mice. Several tumor types were also found that we have never observed in the two parental strains. Our data provide the most direct biological evidence in favor of the viral oncogene theory. Thus, from the presence or absence of expression in early life of splenic gs antigen or virus, we can predict whether or not a tumor is likely to develop later in life. These findings suggest that the genome of endogenous type-C RNA viruses is the major determinant for tumorigenesis although they provide no clues about the factors responsible for the various histological types.
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PMID:Host-gene control of type-C RNA tumor virus expression and tumorigenesis in inbred mice. 435 Nov 80

X-irradiation of outbred Swiss mice resulted in the development of virus-free thymomas. When put in culture, a lymphoblastic cell line (NIXT) expressed neither particles nor infectious virus but supported the growth of pure ecotropic murine leukemia viruses (MuLVs) without generating any envelope recombinant (RM) MuLV in more than 20 months of culture. These cells did not support the growth of RM-MuLVs and completely excluded the entry of all RM-MuLV pseudotypes of murine sarcoma virus, suggesting specific viral interference. Radioimmunocompetition and immunofluorescence assays with broadly reactive anti-MuLV-p30 and -gp70 antisera were negative. However, in immunofluorescence with antisera specifically reactive against RM-MuLV gp70, about 5-20% of the population of parental cells or their clones were positive. NIXT cells treated with this antiserum bound protein A and exhibited complement-dependent cytotoxicity as assessed by several assays. NIXT cells could partially absorb neutralizing antibody specific for RM-MuLVs. Based on radioimmunoprecipitation tests, NIXT cells bore, on the cell surface, a glycosylated protein (gp70) reactive with RM subgroup as well as some group-specific anti-gp70 antisera. The glycoprotein was also found free in the supernates of NIXT cells. Using affinity chromatography, we determined the peptide pattern of the gp70 from NIXT cells to determine its structural relationship to gp70s of other MuLVs. NIXT gp70 was found to be highly related to class III endogenous xenotropic gp70s but, in addition, had peptide characteristics of RM-gp70s. Apparently, NIXT cells code for an unusual gp70 protein in the absence of other MuLV expression. The possible role of this glycoprotein in leukemogenesis is discussed.
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PMID:Detection of a recombinant murine leukemia virus-related glycoprotein on virus-negative thymoma cells. 616 21


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