Effect of the chimeric soluble granulocyte colony-stimulating factor receptor on the proliferation of leukemic blast cells from patients with acute myeloblastic leukemia.
The biological roles of the soluble granulocyte colony-stimulating factor (G-CSF) receptor, which arises as a result of alternative RNA splicing, are as yet unknown. In this study, we examined the in vitro effect of a chimeric protein composed of the extracellular region of a murine G-CSF receptor and the human IgG1 Fc region because a human natural soluble G-CSF receptor was not available. First, we found that this chimeric soluble G-CSF receptor could inhibit the biological activity of G-CSF on normal bone marrow colony formation. Because G-CSF also plays an important role in the proliferation of leukemic blast cells, we next examined the effect of the soluble G-CSF receptor on leukemic blast colony formation in 10 acute myeloblastic leukemia cases. Although G-CSF stimulated the proliferation of leukemic progenitor cells to form leukemic blast colonies, the chimeric soluble G-CSF receptor completely inhibited this stimulatory effect. Furthermore, the chimeric soluble G-CSF receptor also inhibited spontaneous leukemic blast colony formation in two cases. Because a high concentration of G-CSF was observed in the supernatants of leukemic blast cells from these two cases, it seems likely that the soluble G-CSF receptor cut off the autocrine growth mechanism of leukemic blast cells mediated by G-CSF. These findings suggest the possibility that the soluble G-CSF receptor could be used in a clinical application for acute myeloblastic leukemia patients in the future.
Asano
Y
Y
The First Department of Internal Medicine, Faculty of Medicine, Kyushu University, Fukuoka, Japan.
Yokoyama
T
T
Shibata
S
S
Kobayashi
S
S
Shimoda
K
K
Nakashima
H
H
Okamura
S
S
Niho
Y
Y
D000818:Animals; D001752:Blast Crisis / Q000473:pathology*; D002455:Cell Division / Q000187:drug effects; D016179:Granulocyte Colony-Stimulating Factor / Q000494:pharmacology; D006801:Humans; D007141:Immunoglobulin Fc Fragments; D015470:Leukemia, Myeloid, Acute / Q000473:pathology*; D051379:Mice; D016188:Receptors, Granulocyte Colony-Stimulating Factor; D011993:Recombinant Fusion Proteins / Q000737:chemistry / Q000494:pharmacology*
D007141:Immunoglobulin Fc Fragments; D016188:Receptors, Granulocyte Colony-Stimulating Factor; D011993:Recombinant Fusion Proteins; D016179:Granulocyte Colony-Stimulating Factor