Effect of the chimeric soluble granulocyte colony-stimulating factor receptor on the proliferation of leukemic blast cells from patients with acute myeloblastic leukemia.

Abstract

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.

• Authors: Y Asano, T Yokoyama, S Shibata, S Kobayashi, K Shimoda, H Nakashima, S Okamura, Y Niho
• Journal: Cancer research (Cancer Res) Vol. 57 Issue 16 Pg. 3395-7 (Aug 15 1997) ISSN: 0008-5472 [Print] United States
• PMID: 9270003 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Immunoglobulin Fc Fragments
• Receptors, Granulocyte Colony-Stimulating Factor
• Recombinant Fusion Proteins
• Granulocyte Colony-Stimulating Factor

Topics

• Animals
• Blast Crisis (pathology)
• Cell Division (drug effects)
• Granulocyte Colony-Stimulating Factor (pharmacology)
• Humans
• Immunoglobulin Fc Fragments
• Leukemia, Myeloid, Acute (pathology)
• Mice
• Receptors, Granulocyte Colony-Stimulating Factor
• Recombinant Fusion Proteins (chemistry, pharmacology)