Identification of the human analogue of a regulator that induces differentiation in murine leukaemic cells.
We have recently purified murine granulocyte colony-stimulating factor (G-CSF), a regulatory glycoprotein which stimulates granulocyte colony formation from committed murine precursor cells in semi-solid agar cultures. G-CSF is one of a family of colony-stimulating factors that regulate the growth and differentiation of granulocytes and macrophages. 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-2(6)) is able to induce the production of terminally differentiated cells from WEHI-3B and other myeloid leukaemia cell lines. More importantly, G-CSF-containing materials suppress the self-renewal of myeloid leukaemia stem cells in vitro and the leukaemogenicity of treated myeloid leukaemic cells in vivo. 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-beta.
Nicola
N A
NA
Begley
C G
CG
Metcalf
D
D
D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D003115:Colony-Stimulating Factors / Q000302:isolation & purification*; D006098:Granulocytes / Q000166:cytology*; D006801:Humans; D007938:Leukemia / Q000378:metabolism; D051379:Mice; D011956:Receptors, Cell Surface / Q000378:metabolism; D016184:Receptors, Colony-Stimulating Factor; D013045:Species Specificity
D003115:Colony-Stimulating Factors; D011956:Receptors, Cell Surface; D016184:Receptors, Colony-Stimulating Factor