SYNERGISTIC ACTIONS OF STEM-CELL FACTOR AND OTHER BURST-PROMOTING ACTIVITIES ON PROLIFERATION OF CD34(+) HIGHLY PURIFIED BLOOD PROGENITORS EXPRESSING HLA-DR OR DIFFERENT LEVELS OF C-KIT PROTEIN

We studied the synergistic effects of stem cell factor (SCF) and other burst-promoting activities (BPAs) such as interleukin-3 (IL-3), granulocyte-macrophage colony-stimulating factor (GM-CSF), or IL-9 on proliferation of human peripheral blood-derived highly purified progenitors. SCF, IL-3, GMCSF, and IL-9 showed significant BPA when CD34(+)HLA-DR(+) cells were used as the target population, IL-3 exerted the most potent BPA, and GM-CSF supported approximately 40% to 70% of the erythroid burst-forming units that are responsive to IL-3, SCF and IL-9 showed much weaker BPA than that of IL-3 or GM-CSF. Combinations of IL-3 with other BPAs did not show synergistic actions supporting erythroid-burst formation, However, GM-CSF showed a significant additive effect with IL-9 or SCF. When CD34(+)c-kit(high) cells were used as the target, SCF showed a much stronger BPA, Also, a distinct additive effect between SCF and IL-3 or GM-CSF on erythrocyte-containing mixed colony formation was observed. On the other hand, when CD34(+)c-kit(low) cells were used as the target, SCF, IL-3, and GM-CSF could express BPA, In contrast, IL-9 alone failed to support erythroid-burst formation, Because CD34(+)c-kit(high) cells weakly expressed CD34 antigen, these cells appeared to be more mature progenitors than CD34(+)c-kit(low) cells. These results suggest that IL-9 acts on more mature progenitors than those of SCF, IL-3, or GM-CSF and that the primary target of SCF is multipotential progenitors at the very early stage of development. (C) 1994 by The American Society of Hematology.