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)

In contrast to the original B10.BR/SgSn congenic mouse strain, adult mice of the B10.BR/SgLi subline showed a high level of expression of B-tropic ecotropic murine leukemia virus (MuLV). Both B-tropic and N-tropic ecotropic MuLV could be included in cultures of virus-free cell lines derived from embryos of B10.BR/SgLi mice. Both various were also inducible from each of several clonal cell lines and from cultures of F1 embryos of matings of B10.BR/SgLi males with females of strains NFS/N and A/J, which are negative for B-tropic virus. Thus the information for B-tropic MuLV as well as that for N-tropic MuLV was transmitted as a genetic element in the B10.BR/SgLi subline.
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PMID:Induction of B-tropic and N-tropic murine leukemia virus from B10.BR/SgLi mouse embryo cell lines by 5-iodo-2'-deoxyuridine. 22 16

ME26 virus, which was generated by inserting the coding region of the acute avian leukemia-inducing virus E26 into a murine retrovirus vector, encodes a 135-kDa gag-myb-ets fusion protein. Amphotropic murine leukemia virus pseudotypes of ME26 virus induce a high incidence of erythroleukemia 2 to 4 months after injection into newborn NFS/N mice. Spleen cells from the majority of these mice proliferate to high levels in the presence of the erythroid hormone erythropoietin (Epo) and can easily be established as permanent Epo-dependent cell lines. The cell lines contain multiple copies of ME26 viral DNA and express viral message and protein. An Epo receptor mRNA of normal size can be detected in these cells, and binding studies reveal a single class of lower-affinity Epo receptor with an affinity for Epo that is in the range of that previously reported for erythroid cells. The ME26 virus-induced Epo-dependent cell lines, however, appear more immature than previously described erythroid cell lines and more closely resemble early hematopoietic precursor cells, suggesting that the virus may be activating the Epo receptor in hematopoietic cells that do not normally express it. Consistent with this idea, we are able to infect an interleukin-3-dependent myeloid cell line, FDC-P2, with ME26 virus and convert it to Epo dependence. The ME26 virus-infected FDC-P2 cells, even before growth on Epo, showed a large increase in the amount of Epo receptor mRNA. However, no ME26 viral integrations can be detected adjacent to the Epo receptor gene, indicating that the virus is not activating the Epo receptor gene by promoter/enhancer insertion. Our results are more consistent with the hypothesis that the gag-myb-ets-encoded viral fusion protein, which is known to bind DNA, is directly or indirectly activating the expression of the Epo receptor gene in these cells.
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PMID:Induction of erythropoietin responsiveness in murine hematopoietic cells by the gag-myb-ets-containing ME26 virus. 130 43

The BCR/ABL oncogene in chronic myelogenous leukemia produces an activated tyrosine kinase fusion protein (p210). Like other tyrosine kinase oncogenes, BCR/ABL can abrogate the interleukin-3 (IL-3) dependence of lymphoid cell lines. To investigate the ability of BCR/ABL to generate growth factor independence in myeloid cells, the IL-3 dependent myeloid cell line NFS/N1.H7 (H7) was transfected with the p210BCR/ABL-containing plasmid, pGD210. Stable clones A54 and A74 were capable of IL-3 independent growth and tumor formation in syngeneic mice. Relief of growth factor dependence was not mediated by autocrine release of IL-3. The baseline proliferation rate of the BCR/ABL transformed cells was greater than that of the parental H7 cells maximally stimulated by IL-3. Abundant constitutive expression of c-myc, c-jun, and c-fos was observed in the p210BCR/ABL transfectants even in low serum conditions. In contrast, c-myc expression in H7 cells was dependent upon IL-3 stimulation, and neither c-jun nor c-fos was highly expressed following IL-3 stimulation in H7 cells. Thus, BCR/ABL transformation and relief of IL-3 dependence involve not only pathways that can substitute for IL-3 induced growth via tyrosine kinase mediated signals, but also pathways that recruit constitutive c-jun and c-fos expression.
Leukemia 1992 Aug
PMID:BCR/ABL confers growth factor independence upon a murine myeloid cell line. 137 13

A dose and time related effect on neurologic disease expression followed transfer of viral specific cytotoxic T lymphocytes (CTL) to recipient NFS/N mice previously infected at 2 days of age with Cas-Br-M murine leukemia virus. Cas-Br-M MuLV gp70 was expressed in spleen and capillary endothelial cells in the brain and spinal cord of CTL recipients, but the progression of gliosis, vacuolation, and cell death that followed endothelial cell MuLV gp70 expression in unprotected Cas-Br-M MuLV infected mice was interrupted in protected CTL recipients. A direct cytotoxic effect of CTL on infected brain capillary endothelial or neural cells could not be demonstrated. Reduced levels of infectious MuLV and MuLV gp70 expression in brain following syngeneic CTL transfer early in the course of disease suggest that CTL may function by preventing a time-limited interaction of Cas-Br-M MuLV with a susceptible target cell or receptor critical for neurologic disease induction during the perinatal period.
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PMID:Effects of viral specific cytotoxic lymphocytes on the expression of murine leukemia virus induced neurologic disease. 164 77

Southern blot analysis revealed no difference between the DNA from radiation-induced thymic lymphomas and DNA from normal NFS mice. The probes used in the Southern blot analyses used a murine leukemia virus (MuLV) env DNA probe (pXenv), which specifically hybridizes with xenotropic and recombinant viral env genes, and mouse mammary tumor virus (MMTV) DNA probes (MMTV gag-pol, MMTV env, and MMTV LTR). This suggests that radiation leukemogenesis was not associated with gross alteration of the organization of these retroviral genomes. In DNA from radiation-induced thymic lymphoma, there was no indication of gross rearrangement in the common integration site of MuLV, pim-1, or in the common integration sites of MMTV, int-1 and int-2. Dot blot analysis of RNA from radiation-induced thymic lymphomas and normal thymuses demonstrated that there was no substantial difference between them in the expression of retroviral sequences, pim-1, pvt-1, int-1, or int-2, although transcripts that could be hybridized to the retroviral sequences were slightly elevated in some radiation-induced thymic lymphomas. These results show that radiation leukemogenesis does not appear to involve the activation of endogenous type-C and type-B retroviruses.
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PMID:Lack of evidence for the involvement of type-C and type-B retroviruses in radiation leukemogenesis of NFS mice. 169 Apr 35

Severe congenital neutropenia (SCN) is a disorder of myelopoiesis characterized by severe neutropenia or absence of blood neutrophils secondary to a maturational arrest at the level of promyelocytes. We examined peripheral blood mononuclear cells (PBMC) of SCN patients who demonstrated normalization of their blood neutrophil counts in a phase II clinical study with recombinant human granulocyte colony-stimulating factor (rhG-CSF). When stimulated in vitro with bacterial lipopolysaccharides (LPS), PBMC of those SCN patients produced G-CSF activity, as judged by proliferation induction of the murine leukemia cell line, NFS-60. Western and Northern blot analysis showed G-CSF protein and G-CSF-mRNA indistinguishable in size from those of normal controls. We conclude that PBMC of the SCN patients tested are capable of synthesizing and secreting biologically active G-CSF in vitro.
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PMID:Blood mononuclear cells from patients with severe congenital neutropenia are capable of producing granulocyte colony-stimulating factor. 170 35

NFS/N mice infected with neurotropic Cas-Br-M murine leukemia virus (MuLV) at 21 days of age were resistant to neurologic disease and demonstrated MuLV-specific cytotoxic T lymphocyte (CTL) activity in spleen cells after in vitro stimulation. NFS/N mice infected with Cas-Br-M MuLV at 2 days of age failed to generate a significant MuLV-specific CTL response and developed neurologic disease 5-8 weeks later. Protection from neurologic disease transferred with fewer in vitro stimulated immune spleen cells than immune T cells from NFS/N mice infected with Cas-Br-M MuLV at 21 days of age. Cas-Br-M MuLV-specific CTL may play an important role in resistance to the paralytic effects of Cas-Br-M MuLV infection by affecting virus dissemination to the central nervous system.
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PMID:Virus-specific cytotoxic lymphocyte response in a neurotropic murine leukemia virus infection. 184 70

Split-dose X-irradiation efficiently induced Thy-1-positive thymic lymphomas (80%) in intact NFS mice within 12 months after irradiation. A high incidence (67%) of nonthymic lymphomas and leukemias was observed in the thymectomized NFS mice. Development of nonthymic lymphomas and leukemias in these mice started about 2 months later than that of thymic lymphomas and increased significantly 10 months onward after the last irradiation, when the development of thymic lymphomas in intact mice had already come to an end. These nonthymic lymphomas and leukemias involved predominantly the spleen and the mesenteric lymph nodes. Twelve out of 18 lymphomas and leukemias were examined immunocytologically. All of these tumors except one were diagnosed as lymphomas including one plasmacytoma. One case was diagnosed as myelomonocytic leukemia because the leukemic cells were highly positive for nonspecific esterase and negative for chrolacetate esterase. All lymphomas tested were negative for thy-1.2, and five of them expressed surface immunoglobulins. From these results, nonthymic lymphomas developed in thymectomized and X-irradiated NFS mice were classified as B-cell lymphomas probably including non-T/non-B cell lymphomas. Present findings demonstrated that a low incidence of nonthymic lymphomas in intact NFS mice exposed to split-dose X-irradiation should be ascribed to a longer latency since most of the mice died of thymic lymphomas prior to the development of overt nonthymic lymphomas.
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PMID:Development of nonthymic lymphomas in thymectomized NFS mice exposed to split-dose X-irradiation. 209 58

Various strains of mice demonstrate widely differing susceptibility to chemical induction of thymic lymphomas, in both timing and incidence. In AKR mice tumors appear very early and at high incidence after a single dose of N-methyl-N-nitrosourea, while in other strains they appear later and at lower incidences. In an attempt to determine the potential role of AKR ecotropic murine leukemia virus loci in this process, congenic mice of NFS/N background, into which the highly productive ecotropic murine leukemia virus loci AKv-1 or AKv-2 has been transferred, were challenged with N-methyl-N-nitrosourea. Although they had a lower incidence of thymic lymphomas than did the parental donor AKR, the NS.AKv-1 mice had a tumor incidence twice that of NFS/N or NS.AKv-2. However, no difference in timing was noted, and these three strains demonstrated tumor appearance much later than that of AKR/N. It is suggested that the presence of the AKv-1 loci, or a gene of the closely associated genomic region, increases the number of target cells that are susceptible to N-methyl-N-nitrosourea.
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PMID:Role of the AKR gene locus AKv-1 in susceptibility to chemical induction of thymic lymphomas. 216 41

The effects of inserting cellular regulatory sequences from the murine transthyretin (TTR) gene into the Moloney murine leukemia virus (M-MuLV) long terminal repeat (LTR) were investigated. Transthyretin is expressed predominantly in the liver and choroid plexus in adult mice, and TTR upstream regulatory elements were previously shown to potentiate transcription in liver-derived cells. The effects of inserting the TTR distal enhancer and/or promoter-proximal sequences into an M-MuLV LTR lacking its enhancers were measured in three ways. (i) Chimeric LTRs were fused to the bacterial chloramphenicol acetyltransferase gene (cat) and tested for transient gene expression by transfection into liver-derived cells or NIH 3T3 fibroblasts. (ii) Infectious M-MuLV containing an altered LTR [delta Mo + TTR(PD) MuLV) was generated, and infectivity in culture on hepatocyte lines and NIH 3T3 cells was tested. (iii) Infection of delta Mo + TTR(PD) MuLV in vivo was tested by inoculating NFS/N mice and performing in situ hybridization of whole animal sections. Chimeric LTR-cat constructs showed higher levels of cat gene expression in liver-derived cell lines than in NIH 3T3 cells, indicating increased LTR activity in these cells. However, in vitro infection did not show significantly higher infectivity in hepatocytes for delta Mo + TTR(PD) M-MuLV than did wild-type M-MuLV. In vivo, delta Mo + TTR(PD) MuLV showed expression in the same tissues as with wild-type M-MuLV-inoculated mice, i.e., lymphoid organs and the intestines and, additionally, two novel sites not seen in wild-type M-MuLV-inoculated animals. Of 10 mice, 8 showed viral expression in the brain and 3 showed expression in the liver. Thus, insertion of TTR elements into the M-MuLV LTR altered LTR activity both in vitro and in vivo.
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PMID:Substitution of murine transthyretin (prealbumin) regulatory sequences into the Moloney murine leukemia virus long terminal repeat yields infectious virus with altered biological properties. 217 84


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