Interleukin-4 as a growth regulator of clonogenic cells in acute myelogenous leukemia in suspension culture.

Using two complementary culture systems, suspension and clonal cultures, and with a method of graphic display (star diagram), we studied the effects of recombinant human interleukin-4 (IL-4) on leukemic stem cell renewal and differentiation in acute myelogenous leukemia (AML). The interactions between IL-4 and other recombinant human cytokines, granulocyte colony-stimulating factor (G-CSF), granulocyte-macrophage CSF (GM-CSF), macrophage CSF (M-CSF) and interleukins-1 alpha, -2, -3, -5, and -6 were also studied. IL-4 alone had significant effects on both self-renewal and differentiation of blast progenitors in some cases; in clonogenic assay, IL-4 stimulated blast colony formation and in one case IL-4 was the most powerful stimulator among the nine growth factors tested. Star diagrams, constructed using the data from both suspension and clonal cultures, showed that IL-4 could influence the balance between self-renewal and differentiation of clonogenic cells. Negative and positive interactions were detected between IL-4 and other cytokines in suspension culture. These results indicate that IL-4 is a cytokine with a potential role in regulating the growth of myeloid leukemic stem cells, and that IL-4 may be useful in treating selected AML patients.