Abstract
We have extended the study of the effects of antisense oligodeoxynucleotides on hematopoietic colony formation to include the effects of antisense to granulocyte-macrophage colony-stimulating factor (GM-CSF), granulocyte colony-stimulating factor (G-CSF), and macrophage colony-stimulating factor (M-CSF) on bone marrow cultures. GM-CSF antisense and GM-CSF receptor antisense cause an increase in mixed erythroid:nonerythroid colonies and a decrease in mixed nonerythroid colonies, which is an effect opposite to that described previously for erythropoietin (Epo) and Epo receptor antisense. The effect of GM-CSF antisense oligomer is not abrogated by the presence of the ligand in the culture. Antisense oligomers to G-CSF and M-CSF have no effect. When Epo and GM-CSF antisense oligomers are added simultaneously, the effects seem to be independent, with the GM-CSF antisense predominating. These data support the hypothesis of internal autocrine regulation of multipotent hematopoietic precursor cells, and extend the concept to myeloid as well as erythroid differentiation.
