Characterisation of the differential response of normal and CML haemopoietic progenitor cells to macrophage inflammatory protein-1alpha.

2.50
Hdl Handle:
http://hdl.handle.net/10541/88035
Title:
Characterisation of the differential response of normal and CML haemopoietic progenitor cells to macrophage inflammatory protein-1alpha.
Authors:
Dürig, J; Testa, Nydia G; Lord, Brian I; Kasper, C; Chang, James; Telford, Nicholas; Dexter, T Michael; Heyworth, Clare M
Abstract:
The clonogenic cells of chronic myeloid leukaemia (CML), unlike normal haemopoietic colony forming cells (CFC), are resistant to the growth inhibitory effects of the chemokine, macrophage inflammatory protein-1alpha (MIP-1alpha). Here, we tested the hypothesis that MIP-1alpha protects normal, but not CML, CFC from the cytotoxic effects of the cell-cycle active drug cytosine arabinoside (Ara-C). Using a 24-h Ara-C protection assay we showed that MIP-1alpha confers protection to normal CFC but also sensitizes CML CFC to Ara-C. The differential MIP-1alpha responsiveness was not due to a down-regulation of MIP-1alpha receptors on CML CD34+ cells as flow cytometric analysis showed similar binding of a biotinylated MIP-1alpha molecule to normal and CML CD34+ cells. Flow cytometric analysis of the MIP-1alpha receptor subtype CCR-5 revealed comparable CCR-5 expression levels on normal and CML CD34+ cells. Furthermore, culture of CD34+ cells for 10 h in the presence of TNF-alpha resulted in an increased MIP-1alpha receptor expression on both normal and CML CD34+ cells. Our data suggest that the unresponsiveness of CML CFC to the growth inhibitory effect of MIP-1alpha is not caused by a lack of MIP-1alpha receptor or total uncoupling of the MIP-1alpha responsiveness but may be due to an intracellular signalling defect downstream of the receptors.
Affiliation:
CRC Section of Haemopoietic Cell and Gene Therapeutics, Paterson Institute for Cancer Research, Manchester, UK.
Citation:
Characterisation of the differential response of normal and CML haemopoietic progenitor cells to macrophage inflammatory protein-1alpha. 1999, 13 (12):2012-22 Leukemia
Journal:
Leukemia
Issue Date:
Dec-1999
URI:
http://hdl.handle.net/10541/88035
PubMed ID:
10602423
Type:
Article
Language:
en
ISSN:
0887-6924
Appears in Collections:
All Christie Publications ; All Paterson Institute for Cancer Research

Full metadata record

DC FieldValue Language
dc.contributor.authorDürig, Jen
dc.contributor.authorTesta, Nydia Gen
dc.contributor.authorLord, Brian Ien
dc.contributor.authorKasper, Cen
dc.contributor.authorChang, Jamesen
dc.contributor.authorTelford, Nicholasen
dc.contributor.authorDexter, T Michaelen
dc.contributor.authorHeyworth, Clare Men
dc.date.accessioned2009-12-15T16:16:59Z-
dc.date.available2009-12-15T16:16:59Z-
dc.date.issued1999-12-
dc.identifier.citationCharacterisation of the differential response of normal and CML haemopoietic progenitor cells to macrophage inflammatory protein-1alpha. 1999, 13 (12):2012-22 Leukemiaen
dc.identifier.issn0887-6924-
dc.identifier.pmid10602423-
dc.identifier.urihttp://hdl.handle.net/10541/88035-
dc.description.abstractThe clonogenic cells of chronic myeloid leukaemia (CML), unlike normal haemopoietic colony forming cells (CFC), are resistant to the growth inhibitory effects of the chemokine, macrophage inflammatory protein-1alpha (MIP-1alpha). Here, we tested the hypothesis that MIP-1alpha protects normal, but not CML, CFC from the cytotoxic effects of the cell-cycle active drug cytosine arabinoside (Ara-C). Using a 24-h Ara-C protection assay we showed that MIP-1alpha confers protection to normal CFC but also sensitizes CML CFC to Ara-C. The differential MIP-1alpha responsiveness was not due to a down-regulation of MIP-1alpha receptors on CML CD34+ cells as flow cytometric analysis showed similar binding of a biotinylated MIP-1alpha molecule to normal and CML CD34+ cells. Flow cytometric analysis of the MIP-1alpha receptor subtype CCR-5 revealed comparable CCR-5 expression levels on normal and CML CD34+ cells. Furthermore, culture of CD34+ cells for 10 h in the presence of TNF-alpha resulted in an increased MIP-1alpha receptor expression on both normal and CML CD34+ cells. Our data suggest that the unresponsiveness of CML CFC to the growth inhibitory effect of MIP-1alpha is not caused by a lack of MIP-1alpha receptor or total uncoupling of the MIP-1alpha responsiveness but may be due to an intracellular signalling defect downstream of the receptors.en
dc.language.isoenen
dc.subjectHaematopoietic Stem Cellsen
dc.subjectLeukaemiaen
dc.subjectCancer Stem Cellsen
dc.subjectTumour Necrosis Factor-alphaen
dc.subject.meshAdolescent-
dc.subject.meshAdult-
dc.subject.meshAged-
dc.subject.meshCell Adhesion-
dc.subject.meshCell Cycle-
dc.subject.meshChemokine CCL3-
dc.subject.meshChemokine CCL4-
dc.subject.meshChild-
dc.subject.meshCytarabine-
dc.subject.meshFemale-
dc.subject.meshFluorescent Antibody Technique-
dc.subject.meshHematopoietic Stem Cells-
dc.subject.meshHumans-
dc.subject.meshLeukemia, Myelogenous, Chronic, BCR-ABL Positive-
dc.subject.meshMacrophage Inflammatory Proteins-
dc.subject.meshMale-
dc.subject.meshMiddle Aged-
dc.subject.meshNeoplastic Stem Cells-
dc.subject.meshReceptors, CCR5-
dc.subject.meshTumor Necrosis Factor-alpha-
dc.titleCharacterisation of the differential response of normal and CML haemopoietic progenitor cells to macrophage inflammatory protein-1alpha.en
dc.typeArticleen
dc.contributor.departmentCRC Section of Haemopoietic Cell and Gene Therapeutics, Paterson Institute for Cancer Research, Manchester, UK.en
dc.identifier.journalLeukemiaen
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