Altered development and cytokine responses of myeloid progenitors in the absence of transcription factor, interferon consensus sequence binding protein.

2.50
Hdl Handle:
http://hdl.handle.net/10541/91365
Title:
Altered development and cytokine responses of myeloid progenitors in the absence of transcription factor, interferon consensus sequence binding protein.
Authors:
Scheller, Marina; Foerster, John; Heyworth, Clare M; Waring, Jeffrey F; Löhler, Jurgen; Gilmore, Gary L; Shadduck, Richard K; Dexter, T Michael; Horak, Ivan
Abstract:
Mice deficient for the transcription factor, interferon consensus sequence binding protein (ICSBP), are immunodeficient and develop disease symptoms similar to human chronic myeloid leukemia (CML). To elucidate the hematopoietic disorder of ICSBP(-/-) mice, we investigated the growth, differentiation, and leukemogenic potential of ICSBP(-/-) myeloid progenitor cells in vitro, as well as by cell-transfers in vivo. We report that adult bone marrow, as well as fetal liver of ICSBP-deficient mice harbor increased numbers of progenitor cells, which are hyperresponsive to both granulocyte macrophage colony-stimulating factor (GM-CSF) and G-CSF in vitro. In contrast, their response to M-CSF is strongly reduced and, surprisingly, ICSBP(-/-) colonies formed in the presence of M-CSF are mostly of granulocytic morphology. This disproportional differentiation toward cells of the granulocytic lineage in vitro parallels the expansion of granulocytes in ICSBP(-/-) mice and correlates with a 4-fold reduction of M-CSF receptor expressing cells in bone marrow. Cell transfer studies showed an intrinsic leukemogenic potential and long-term reconstitution capability of ICSBP(-/-) progenitors. Further experiments demonstrated strongly reduced adhesion of colony-forming cells from ICSBP(-/-) bone marrow to fibronectin. In summary, ICSBP(-/-) myeloid progenitor cells share several abnormal features with CML progenitors, suggesting that the distal parts of signaling pathways of these two disorders are overlapping.
Affiliation:
Abteilung für Molekulare Genetik, Forschungsinstitut für Molekulare Pharmakologie, und Universitätsklinikum Benjamin Franklin, Freie Universität Berlin, Berlin, Germany.
Citation:
Altered development and cytokine responses of myeloid progenitors in the absence of transcription factor, interferon consensus sequence binding protein. 1999, 94 (11):3764-71 Blood
Journal:
Blood
Issue Date:
1-Dec-1999
URI:
http://hdl.handle.net/10541/91365
PubMed ID:
10572090
Type:
Article
Language:
en
ISSN:
0006-4971
Appears in Collections:
All Paterson Institute for Cancer Research

Full metadata record

DC FieldValue Language
dc.contributor.authorScheller, Marinaen
dc.contributor.authorFoerster, Johnen
dc.contributor.authorHeyworth, Clare Men
dc.contributor.authorWaring, Jeffrey Fen
dc.contributor.authorLöhler, Jurgenen
dc.contributor.authorGilmore, Gary Len
dc.contributor.authorShadduck, Richard Ken
dc.contributor.authorDexter, T Michaelen
dc.contributor.authorHorak, Ivanen
dc.date.accessioned2010-02-08T13:35:12Z-
dc.date.available2010-02-08T13:35:12Z-
dc.date.issued1999-12-01-
dc.identifier.citationAltered development and cytokine responses of myeloid progenitors in the absence of transcription factor, interferon consensus sequence binding protein. 1999, 94 (11):3764-71 Blooden
dc.identifier.issn0006-4971-
dc.identifier.pmid10572090-
dc.identifier.urihttp://hdl.handle.net/10541/91365-
dc.description.abstractMice deficient for the transcription factor, interferon consensus sequence binding protein (ICSBP), are immunodeficient and develop disease symptoms similar to human chronic myeloid leukemia (CML). To elucidate the hematopoietic disorder of ICSBP(-/-) mice, we investigated the growth, differentiation, and leukemogenic potential of ICSBP(-/-) myeloid progenitor cells in vitro, as well as by cell-transfers in vivo. We report that adult bone marrow, as well as fetal liver of ICSBP-deficient mice harbor increased numbers of progenitor cells, which are hyperresponsive to both granulocyte macrophage colony-stimulating factor (GM-CSF) and G-CSF in vitro. In contrast, their response to M-CSF is strongly reduced and, surprisingly, ICSBP(-/-) colonies formed in the presence of M-CSF are mostly of granulocytic morphology. This disproportional differentiation toward cells of the granulocytic lineage in vitro parallels the expansion of granulocytes in ICSBP(-/-) mice and correlates with a 4-fold reduction of M-CSF receptor expressing cells in bone marrow. Cell transfer studies showed an intrinsic leukemogenic potential and long-term reconstitution capability of ICSBP(-/-) progenitors. Further experiments demonstrated strongly reduced adhesion of colony-forming cells from ICSBP(-/-) bone marrow to fibronectin. In summary, ICSBP(-/-) myeloid progenitor cells share several abnormal features with CML progenitors, suggesting that the distal parts of signaling pathways of these two disorders are overlapping.en
dc.language.isoenen
dc.subjectCancerous Gene Expression Regulationen
dc.subjectHaematopoietic Stem Cellsen
dc.subjectBCR-ABL Positive Chronic Myelogenous Leukemiaen
dc.subject.meshAdult-
dc.subject.meshAnimals-
dc.subject.meshCells, Cultured-
dc.subject.meshCytokines-
dc.subject.meshGene Expression Regulation-
dc.subject.meshGene Expression Regulation, Neoplastic-
dc.subject.meshHematopoietic Stem Cells-
dc.subject.meshHumans-
dc.subject.meshInterferon Regulatory Factors-
dc.subject.meshInterferons-
dc.subject.meshLeukemia, Myelogenous, Chronic, BCR-ABL Positive-
dc.subject.meshLeukopoiesis-
dc.subject.meshMice-
dc.subject.meshRepressor Proteins-
dc.titleAltered development and cytokine responses of myeloid progenitors in the absence of transcription factor, interferon consensus sequence binding protein.en
dc.typeArticleen
dc.contributor.departmentAbteilung für Molekulare Genetik, Forschungsinstitut für Molekulare Pharmakologie, und Universitätsklinikum Benjamin Franklin, Freie Universität Berlin, Berlin, Germany.en
dc.identifier.journalBlooden

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