Regulation of the genes for interleukin-6 and granulocyte-macrophage colony stimulating factor by different inducers of differentiation in myeloid leukemic cells.

Different clones of myeloid leukemic cells can be induced to differentiate to mature macrophages and/or granulocytes by hematopoietic regulatory proteins and by other compounds. We now show that induction of differentiation in different clones of myeloid leukemic cells with the normal hematopoietic proteins granulocyte-colony stimulating factor (G-CSF), granulocyte-macrophage colony stimulating factor (GM-CSF), or interleukin 3 and by compounds such as dexamethasone or cytosine arabinoside (ara C) induces the expression of genes for the myeloid differentiation inducing protein MGI-2 that we have shown is interleukin 6 (IL-6) and for GM-CSF. We have previously shown that induction of differentiation with interleukin-1, IL-6, or bacterial lipopolysaccharide (LPS) also induces IL-6 and GM-CSF gene expression. Treatment of these leukemic clones with hematopoietic proteins that do not induce differentiation did not induce IL-6 or GM-CSF gene expression. The results indicate that induction of IL-6 and GM-CSF gene expression is part of the normal differentiation program in myeloid cells and support our previous evidence that there is transregulation of gene expression between different hematopoietic regulatory proteins.