Effects of recombinant IL-3, GM-CSF, and G-CSF on proliferation of leukemic clonogenic cells in short-term and long-term cultures

To further define the growth factors required for the in vitro proliferation of acute myeloblastic leukemic (AML) cells, we have compared the ability of recombinant interleukin-3 (IL-3), granulocyte-macrophage colony stimulating factor (GM-CSF), and granulocyte colony stimulating factor (G-CSF) to support growth of AML colony forming cells (AML-CFU). IL-3, GM-CSF, and G-CSF are active as single growth factors in short-term colony cultures and have additive effects when used in combination in some cases. The effects of these CSFs on the proliferation of AML cells in long-term cell-suspension cultures were also investigated. These cultures provide an estimate of the 'self-renewal' capacity and long-term proliferation potential of AML cells. There was considerably heterogeneity with regard to the effects of individual growth factors, but in general, IL-3, GM-CSF, and G-CSF promoted self-renewal of AML cells, and combinations tended to be more effective in supporting long-term survival of AML-CFU. There was evidence of gradual differentiation, but this was evident in control cells and did not appear to be accelerated by CSF treatment. These results of short-term and long-term cultures indicate that each of the CSFs tested can be used by AML cells to support proliferation. The lack of evidence that the CSFs enhance in vitro differentiation does not suggest they will be valuable as therapeutic differentiation agents.