Identification of the human analogue of a regulator that induces differentiation in murine leukaemic cells

Abstract

We have recently purified murine granulocyte colony-stimulating factor (G-CSF)¹, a regulatory glycoprotein which stimulates granulocyte colony formation from committed murine precursor cells in semi-solid agar cultures². G-CSF is one of a family of colony-stimulating factors that regulate the growth and differentiation of granulocytes and macrophages^3–5. While the other murine CSFs (granulocyte–macrophage (GM)-CSF, macrophage (M)-CSF and multi-CSF) show little or no differentiation-inducing activity on murine myelomonocytic leukaemia cell lines, G-CSF (or MGI-2⁶) is able to induce the production of terminally differentiated cells from WEHI-3B and other myeloid leukaemia cell lines^6–8. More importantly, G-CSF-containing materials suppress the self-renewal of myeloid leukaemia stem cells in vitro⁸ and the leukaemogenicity of treated myeloid leukaemic cells in vivo^9–13. It is important to identify the human analogue of murine G-CSF so that its effectiveness on human myeloid leukaemia cells can be assessed. Here we show that an analogue of G-CSF does exist among the CSFs produced by human cells and that the murine and human molecules show almost complete biological and receptor-binding cross-reactivities to normal and leukaemic murine or human cells. The human G-CSF analogue is identified as a species of CSF that we have previously described as CSF-β (ref. 14).