Dissociation of the proliferation and differentiation stimuli of granulocyte colony-stimulating factor (G-CSF).
One proposed therapeutic application of granulocyte colony-stimulating factor (G-CSF) is in differentiation induction therapy of myelodysplastic states (MDS) or acute myeloid leukemia (AML). G-CSF however has a substantial growth including effect which limits its potential as a differentiation inducing agent. We have therefore made a systematic search for agents which might restrain the proliferative effects of G-CSF whilst retaining the differentiation stimulus. Of all the agents we have tested on human bone marrow progenitor cells: (6-thioguanine, all-trans retinoic acid, vincristine, recombinant human alpha-2b and gamma-interferon) only the latter abolished the stimulation of cell growth and retained, or possibly increased, the differentiation effect of G-CSF. The antiproliferative drugs 6-thioguanine and vincristine both antagonized the neutrophil-granulocyte differentiation inducing action of G-CSF. Retinoic acid and alpha-2b interferon both had weak effects on proliferation and failed to enhance differentiation. These results suggest that it may be possible, by combining G-CSF with a suitable second agent, to utilize its substantial differentiation inducing effect without incurring the potentially hazardous effects of increased leukemic cell growth.
Irvine
A E
AE
Department of Haematology, Queen's University of Belfast, U.K.
Berney
J J
JJ
Francis
G E
GE
D002454:Cell Differentiation / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D003115:Colony-Stimulating Factors / Q000494:pharmacology*; D016179:Granulocyte Colony-Stimulating Factor; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D006133:Growth Substances / Q000494:pharmacology; D006801:Humans; D007371:Interferon-gamma / Q000494:pharmacology; D007377:Interleukin-3 / Q000494:pharmacology; D009190:Myelodysplastic Syndromes / Q000628:therapy
D003115:Colony-Stimulating Factors; D006133:Growth Substances; D007377:Interleukin-3; D016179:Granulocyte Colony-Stimulating Factor; D007371:Interferon-gamma; D016178:Granulocyte-Macrophage Colony-Stimulating Factor