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dc.contributor.authorDürig, J
dc.contributor.authorTesta, Nydia G
dc.contributor.authorLord, Brian I
dc.contributor.authorKasper, C
dc.contributor.authorChang, James
dc.contributor.authorTelford, Nicholas
dc.contributor.authorDexter, T Michael
dc.contributor.authorHeyworth, Clare M
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.
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
html.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.


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