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-1α (MIP-1α). Here, we tested the hypothesis that MIP-1α 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-1α confers protection to normal CFC but also sensitises CML CFC to Ara-C. The differential MIP-1α responsiveness was not due to a down-regulation of MIP-1α receptors on CML CD34+ cells as flow cytometric analysis showed similar binding of a biotinylated MIP-1α molecule to normal and CML CD34+ cells. Flow cytometric analysis of the MIP-1α 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-α resulted in an increased MIP-1α 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-1α is not caused by a lack of MIP-1α receptor or total uncoupling of the MIP-1α responsiveness but may be due to an intracellular signalling defect downstream of the receptors.
This is a preview of subscription content, access via your institution
Access options
Subscribe to this journal
Receive 12 print issues and online access
$259.00 per year
only $21.58 per issue
Buy this article
- Purchase on Springer Link
- Instant access to full article PDF
Prices may be subject to local taxes which are calculated during checkout
Similar content being viewed by others
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Dürig, J., Testa, N., Lord, B. et al. Characterisation of the differential response of normal and CML haemopoietic progenitor cells to macrophage inflammatory protein-1α. Leukemia 13, 2012–2022 (1999). https://doi.org/10.1038/sj.leu.2401610
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1038/sj.leu.2401610
Keywords
This article is cited by
-
Traumatic inflammatory response: pathophysiological role and clinical value of cytokines
European Journal of Trauma and Emergency Surgery (2023)
-
Mast cell deficiency prevents BCR::ABL1 induced splenomegaly and cytokine elevation in a CML mouse model
Leukemia (2023)
-
NOD/SCID repopulating cells but not LTC-IC are enriched in human CD34+ cells expressing the CCR1 chemokine receptor
Leukemia (2001)
-
Biological effects of stroma-derived factor-1α on normal and CML CD34+ haemopoietic cells
Leukemia (2000)