Characterisation of the differential response of normal and CML haemopoietic progenitor cells to macrophage inflammatory protein-1alpha.
Testa, Nydia G
Lord, Brian I
Dexter, T Michael
Heyworth, Clare M
AffiliationCRC Section of Haemopoietic Cell and Gene Therapeutics, Paterson Institute for Cancer Research, Manchester, UK.
MetadataShow full item record
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.
CitationCharacterisation of the differential response of normal and CML haemopoietic progenitor cells to macrophage inflammatory protein-1alpha. 1999, 13 (12):2012-22 Leukemia
- Abl protein kinase abrogates the response of multipotent haemopoietic cells to the growth inhibitor macrophage inflammatory protein-1 alpha.
- Authors: Wark G, Heyworth CM, Spooncer E, Czaplewski L, Francis JM, Dexter TM, Whetton AD
- Issue date: 1998 Mar 12
- MCP-1, not MIP-1alpha, is the endogenous chemokine that cooperates with TGF-beta to inhibit the cycling of primitive normal but not leukemic (CML) progenitors in long-term human marrow cultures.
- Authors: Cashman JD, Eaves CJ, Sarris AH, Eaves AC
- Issue date: 1998 Oct 1
- Macrophage inflammatory protein-1 alpha receptors are present on cells enriched for CD34 expression from patients with chronic myeloid leukemia.
- Authors: Chasty RC, Lucas GS, Owen-Lynch PJ, Pierce A, Whetton AD
- Issue date: 1995 Dec 1
- Macrophage-inflammatory protein-1alpha receptor expression on normal and chronic myeloid leukemia CD34+ cells.
- Authors: Nicholls SE, Lucas G, Graham GJ, Russell NH, Mottram R, Whetton AD, Buckle AM
- Issue date: 1999 May 15
- Expression of macrophage inflammatory protein-1 receptors in human CD34(+) hematopoietic cells and their modulation by tumor necrosis factor-alpha and interferon-gamma.
- Authors: Dürig J, de Wynter EA, Kasper C, Cross MA, Chang J, Testa NG, Heyworth CM
- Issue date: 1998 Nov 1