Effects of recombinant human granulocyte colony stimulating factor (rG-CSF) on murine myeloid leukemia: stimulation of proliferation of leukemic cells in vitro and inhibition of development of leukemia in vivo.
We have established an experimental murine myeloid leukemia model and investigated the effects of recombinant granulocyte colony stimulating factor (rG-CSF) on myeloid leukemia in vitro and in vivo. rG-CSF stimulated colony formation by the leukemic cells in semisolid agar medium, and exponential growth of the clonogenic cells in suspension medium. Thus, rG-CSF was able to stimulate both the differentiation and self-renewal processes of the leukemic stem cells in vitro. However, 14 consecutive daily injections of rG-CSF prolonged the mean survival time of the mice implanted with the leukemic cells. This effect of rG-CSF was accompanied by a delay in the emergence of the blast cells in peripheral blood and by a decreased blast population in the spleen, suggesting that development of leukemia was suppressed in the rG-CSF-treated-mice. The prolongation of the survival time by rG-CSF was more evident when rG-CSF was administered in therapeutic combination with cyclophosphamide. These results indicate that the effect of rG-CSF on the development of leukemia is not exactly predicted from in vitro experiments.
Tamura
M
M
Fuji-Gotemba Laboratory, Chugai Pharmaceutical Company, Ltd., Gotemba, Japan.
Hattori
K
K
Ono
M
M
Hata
S
S
Hayata
I
I
Asano
S
S
Bessho
M
M
Hirashima
K
K
D000818:Animals; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D003115:Colony-Stimulating Factors / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D003520:Cyclophosphamide / Q000008:administration & dosage; D016179:Granulocyte Colony-Stimulating Factor; D006098:Granulocytes / Q000187:drug effects*; D007942:Leukemia, Experimental / Q000473:pathology*; D007951:Leukemia, Myeloid / Q000188:drug therapy / Q000473:pathology*; D051379:Mice; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D014407:Tumor Cells, Cultured
D003115:Colony-Stimulating Factors; D011994:Recombinant Proteins; D016179:Granulocyte Colony-Stimulating Factor; D003520:Cyclophosphamide