Characterisation of the differential response of normal and CML haemopoietic progenitor cells to macrophage inflammatory protein-1alpha.
Dürig, J Testa, Nydia G Lord, Brian I Kasper, C Chang, James Telford, Nicholas Dexter, T Michael Heyworth, Clare M
Dürig, J
Testa, Nydia G
Lord, Brian I
Kasper, C
Chang, James
Telford, Nicholas
Dexter, T Michael
Heyworth, Clare M
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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.
Description
Date
1999-12
Publisher
Keywords
Haematopoietic Stem Cells
Leukaemia
Cancer Stem Cells
Tumour Necrosis Factor-alpha
Leukaemia
Cancer Stem Cells
Tumour Necrosis Factor-alpha
Type
Article
Citation
Characterisation of the differential response of normal and CML haemopoietic progenitor cells to macrophage inflammatory protein-1alpha. 1999, 13 (12):2012-22 Leukemia