Characterisation of the differential response of normal and CML haemopoietic progenitor cells to macrophage inflammatory protein-1alpha.
Authors
Dürig, JTesta, Nydia G
Lord, Brian I
Kasper, C
Chang, James
Telford, Nicholas
Dexter, T Michael
Heyworth, Clare M
Affiliation
CRC Section of Haemopoietic Cell and Gene Therapeutics, Paterson Institute for Cancer Research, Manchester, UK.Issue Date
1999-12
Metadata
Show full item recordAbstract
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.Citation
Characterisation of the differential response of normal and CML haemopoietic progenitor cells to macrophage inflammatory protein-1alpha. 1999, 13 (12):2012-22 LeukemiaJournal
LeukemiaPubMed ID
10602423Type
ArticleLanguage
enISSN
0887-6924Related articles
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