The response of normal and chronic myeloid leukemia (CML), CD34+cells to human macrophage inflammatory protein-1α (MIP-1α or LD78) was assessed. In tritiated thymidine incorporation assays, stem cell factor plus granulocyte- macrophage colony-stimulating factor stimulated thymidine incorporation in normal CD34+cells was reduced to 72% of control values in the presence of MIP-1α, whereas incorporation by CML CD34+cells exposed to the same factors was not altered. In clonogenic assays, the presence of MIP-1α gave a level of colony formation that was 71% of control values for normal progenitor cells, whereas for CML CD34+cells colony formation was enhanced by 25%. These results suggest that, in vitro, CML progenitor cells are relatively refractory to the growth inhibitory effects of MIP-1α. Using flow cytometry, the specific binding of a biotinylated human MIP-1α/avidin fluorescein (FITC) conjugate to normal and CML mononuclear and CD34+cell populations was quantified. The data indicate that (for both normal and CML CD34+cells) there was a single population of cells that express cell surface receptors for MIP-1α and this receptor expression was independent of cell cycle status. CML progenitor cells may be refractory to the effects of MIP-1α as a result of events downstream from receptor expression.
|Number of pages||8|
|Publication status||Published - 1 Dec 1995|