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.

2.50
Hdl Handle:
http://hdl.handle.net/10541/101877
Title:
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.
Authors:
Just, Ursula; Katsuno, M; Stocking, C; Spooncer, Elaine; Dexter, T Michael
Abstract:
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.
Affiliation:
Cancer Research Campaign Department of Experimental Haematology, Paterson Institute for Cancer Research, Christie Hospital, Manchester, UK.
Citation:
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. 1993, 9 (1):41-55 Growth Factors
Journal:
Growth Factors
Issue Date:
1993
URI:
http://hdl.handle.net/10541/101877
DOI:
10.3109/08977199308991581
PubMed ID:
8102237
Type:
Article
Language:
en
ISSN:
0897-7194
Appears in Collections:
All Paterson Institute for Cancer Research

Full metadata record

DC FieldValue Language
dc.contributor.authorJust, Ursulaen
dc.contributor.authorKatsuno, Men
dc.contributor.authorStocking, Cen
dc.contributor.authorSpooncer, Elaineen
dc.contributor.authorDexter, T Michaelen
dc.date.accessioned2010-06-07T17:17:36Z-
dc.date.available2010-06-07T17:17:36Z-
dc.date.issued1993-
dc.identifier.citationTargeted 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. 1993, 9 (1):41-55 Growth Factorsen
dc.identifier.issn0897-7194-
dc.identifier.pmid8102237-
dc.identifier.doi10.3109/08977199308991581-
dc.identifier.urihttp://hdl.handle.net/10541/101877-
dc.description.abstractTo 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.en
dc.language.isoenen
dc.subjectHaematopoietic Stem Cellsen
dc.subjectHaematopoietic Stem Cell Transplantationen
dc.subjectExperimental Leukaemiaen
dc.subject.meshAnimals-
dc.subject.meshCell Differentiation-
dc.subject.meshCell Division-
dc.subject.meshCell Line-
dc.subject.meshCell Transformation, Neoplastic-
dc.subject.meshColony-Forming Units Assay-
dc.subject.meshFemale-
dc.subject.meshGenetic Vectors-
dc.subject.meshHematopoietic Stem Cell Transplantation-
dc.subject.meshHematopoietic Stem Cells-
dc.subject.meshInterleukin-3-
dc.subject.meshLeukemia, Experimental-
dc.subject.meshMale-
dc.subject.meshMice-
dc.subject.meshMyeloproliferative Disorders-
dc.subject.meshRetroviridae-
dc.titleTargeted 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.en
dc.typeArticleen
dc.contributor.departmentCancer Research Campaign Department of Experimental Haematology, Paterson Institute for Cancer Research, Christie Hospital, Manchester, UK.en
dc.identifier.journalGrowth Factorsen
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