MACROPHAGE INFLAMMATORY PROTEIN-1-ALPHA RECEPTORS ARE PRESENT ON CELLS ENRICHED FOR CD34 EXPRESSION FROM PATIENTS WITH CHRONIC MYELOID-LEUKEMIA

The response of normal and chronic myeloid leukemia (CML), CD34(+) cells to human macrophage inflammatory protein-1 alpha (MIP-1 alpha 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-1 alpha, whereas incorporation by CML CD34(+) cells exposed to the same factors was not altered. In clonogenic assays, the presence of MIP-1 alpha 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-1 alpha. Using flow cytometry, the specific binding of a biotinylated human MIP-1 alpha/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 calls that express cell surface receptors for MIP-1 alpha and this receptor expression was independent of cell cycle statue. CML progenitor cells may be refractory to the effects of MIP-1 alpha as a result of events downstream from receptor expression. (C) 1995 by The American Society of Hematology.