Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: DrugBank:EXPT01586 (G418)
 2,237 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

To measure the effect of endogenous IL-3 (Multi-CSF) expression on hematopoietic cells in vivo, we have infected several kinds of hematopoietic cell populations with retroviral vectors carrying the IL-3 gene (M3MuV) in vitro and injected the virus-producing cells into mice to "target" the virus to sites of hematopoiesis. Mast cell lines (Elut cells) or multipotent cell lines (FDC-Pmix) were infected with MPSV-based replication defective retroviral vectors carrying either the neomycin resistance gene alone (M3neoV) or the neomycin gene plus the IL-3 gene (M3MuV). These cell lines produced infective retroviral particles consisting of the replication defective vectors and helper virus constitutively produced by the target cell populations. Irradiated and non-irradiated virus-producing Elut cells and the virus-producing FDC-Pmix cells were transplanted into syngeneic mice to "target" virus infection to the sites of hemopoiesis. Control mice injected with M3neoV-producing cells did not develop a disease up to 6 months following transplantation, whereas mice injected with M3MuV-producing cells developed a myeloproliferative disease within 3 months. Hematopoietic cell lines were rescued from diseased and control mice. In all cases these cell lines were of host origin. Cell lines derived from control mice were of basophil/mast cell morphology only, and required IL-3 for their continued proliferation (similar to cell lines derived from uninfected animals), whereas the cell lines generated from spleen and bone marrow cells of host mice with myeloproliferative disease carried the M3MuV vector, were G418 resistant and IL-3 independent. The biologic properties of M3MuV infected host derived cell lines varied considerably. Some were multipotential and could be induced to differentiate in response to stromal cells and serum factors, others were more restricted to the granulocyte/macrophage lineage but were also differentiation inducible, and some were blocked in differentiation at the myeloblast/promyelocyte stage. We conclude that the injected donor cells acted as "infectious centers" to facilitate the infection of host hematopoietic cells with the M3MuV vector. Our results indicate that the "targeted" in vivo infection of primitive hematopoietic cells with M3MuV can initiate the immortalization and leukaemogenesis of multipotential and lineage restricted progenitor cells.
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PMID:Targeted in vivo infection with a retroviral vector carrying the interleukin-3 (multi-CSF) gene leads to immortalization and leukemic transformation of primitive hematopoietic progenitor cells. 810 37

Although PDGF is not a primary hematopoietic cytokine, effects in hematopoietic cell cultures have been reported. We recently described responses of multilineage hematopoietic precursors to PDGF. The effects were shown to be neutralized by antibody to IL-1 beta and mediated by marrow macrophages that expressed PDGF receptor RNA and responded to PDGF by upregulation of IL-1 RNA. The present study was performed to determine whether constitutive expression of PDGF by hematopoietic cells would have hematopoietic consequences in vivo. Retroviral vectors containing a PDGF-B gene were constructed and infected into normal marrow cells. Irradiated mice reconstituted with infected cells consistently developed a lethal myeloproliferative syndrome with anemia, neutrophilia and monocytosis, declining hematopoiesis in marrow with shift to the spleen, and extensive infiltration of immature hematopoietic cells into the parenchymal organs and connective tissues. In addition to PDGF, the retroviral constructs expressed a neo resistance marker. Phenotypic expression patterns in fibroblasts and in hematopoietic colony-forming cells in vitro were consistent with a significant degree of interaction between the two expressed inserts. Moreover, selection of infected cells for G418 resistance significantly reduced not only the number of infected reconstituting cells but also the intensity of the evoked syndrome in vivo. The observations have important implications for projected gene therapy protocols, and identify a novel potential pathway to myeloproliferative disease.
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PMID:Overexpression of PDGF-B in murine hematopoietic cells induces a lethal myeloproliferative syndrome in vivo. 830 75

Chronic myelogenous leukemia (CML) is a clonal myeloproliferative disease of transformed hematopoietic progenitor cells. It is now clear that the chimeric bcr/abl P210(bcr/abl) fusion protein, which is generated by the reciprocal translocation t (9; 22), inhibits apoptosis and increase proliferation. P210(bcr/abl) plays a central role in the pathophysiology of CML. The purpose of this study was to construct a cell line model that bcr/abl expression can be regulated by Tet-off inducing-expression-system. The full-length b3a2 bcr/abl cDNA was subcloned into the pTRE2hyg expression vector to construct the pT2-P210 plasmid. 293 cells were firstly transfected with Tet-off plasmid and the clone that the Tet-off system can work effectively after transfected with pTRE2hyg-LUC was selected by luciferase activity assay. The pT2-P210 plasmid was then transfected into the selected clone and cells were then selected for hygromycin B and G418 resistance. The results showed that individual subclones expressing bcr/abl after withdrawing doxycycline were 293pT2-P210 cell line. In conclusion, selected 293pT2-P210 cells are cells that bcr/abl expression can be regulated by Tet-off inducing-expression-system. They are suitable thoroughly to study the function of bcr/abl fusion gene and its signal regulation mechanism.
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PMID:[Construction of 293pT2-P210 cell line enables expression of bcr/abl to be regulated by Tet-off inducing-expression-system]. 1749 20