G-CSF: Its relationship to leukemia differentiation-inducing activity and other hemopoietic regulators

Abstract

The murine myelomonocytic leukemia WEHI-3B exists as differentiation-inducible (D⁺) and noninducible (D⁻) cell lines. Both lines produce a CSF species that stimulates exclusively the formation of neutrophil granulocyte colonies. This G-CSF copurifies with a mast cell growth factor but can be separated from M- and GM-CSF. NZB bone marrow is unresponsive to G-CSF stimulation. WEHI-3B D⁺ cells can be induced to terminal granulocyte differentiation by a factor present in murine and human postendotoxin serum that is different from G-CSF present in WEHI-3B D⁺ or D⁻ CM since the latter has little or no leukemia differentiation-inducing activity. Endotoxin treatment of C. parvum primed mice leads to simultaneous induction of serum activities with selective action on myeloid leukemic cells, a serum differentiation inducing activity and a leukemic colony inhibitory activity. These factors act synergistically to block leukemic stem cell self-renewal. The results suggest that a variety of inducible factors may have potent and selective antileukemic activity.