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- Title
Differential effect of interferon α on chronic myelogenous leukaemia and normal haematopoietic progenitors in a stromal cell co-culture context: role of the flt3 ligand.
- Authors
Solanilla, A.; El Andaloussi, A.; Grosset, C.; Duchez, P.; Mossalayi, M. D.; Mahon, F. X.; Reiffers, J.; Marit, G.; Ripoche, J.
- Abstract
Interferon alpha (IFN-α) is used to treat chronic myelogenous leukaemia (CML) patients. However, its target(s) remain(s) unknown. One possibility is that there is a differing sensitivity of the leukaemic from the normal colony-forming cell (CFC) compartments to IFN-α. Co-cultures of progenitors with stromal cells provide a valuable tool to dissect direct and indirect activities of IFN-α. In this study, we have used endothelial cells (EC) as a source of stromal cells. In co-cultures of normal progenitors with EC, IFN-α increased the generation of clonogenic cells, mainly via an increased production of flt3 ligand (FL) by EC. In contrast, in co-cultures of CML progenitors with EC, IFN-α inhibited the generation of clonogenic cells, mainly by direct inhibition on the progenitors, the up-regulation of FL production by stromal cells being unable to compensate for the direct inhibitory effects of IFN-α. These data provide evidence for a differential effect of IFN-α on the growth of CML and normal CFC cells in a stromal context and suggest that an alteration in the response of CML progenitor cells to FL is important in the explanation of this differential effect.
- Subjects
LEUKEMIA treatment; MYELOID leukemia; THERAPEUTIC use of interferons; HEMATOPOIESIS
- Publication
British Journal of Haematology, 2000, Vol 109, Issue 2, p382
- ISSN
0007-1048
- Publication type
Article
- DOI
10.1046/j.1365-2141.2000.01917.x