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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
Author(s) -
Solanilla A.,
El Andaloussi A.,
Grosset C.,
Duchez P.,
Mossalayi M. D.,
Mahon F. X.,
Reiffers J.,
Marit G.,
Ripoche J.
Publication year - 2000
Publication title -
british journal of haematology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.907
H-Index - 186
eISSN - 1365-2141
pISSN - 0007-1048
DOI - 10.1046/j.1365-2141.2000.01917.x
Subject(s) - progenitor cell , stromal cell , haematopoiesis , context (archaeology) , clonogenic assay , biology , immunology , cancer research , chronic myelogenous leukemia , stem cell , interferon , microbiology and biotechnology , cell culture , leukemia , genetics , paleontology
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.