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Effect of the Chimeric Soluble Granulocyte Colony-stimulating Factor Receptor on the Proliferation of Leukemic Blast Cells from Patients with Acute Myeloblastic Leukemia¹

The First Department of Internal Medicine, Faculty of Medicine, Kyushu University, 3-1-1 Maidashi, Higashi-ku. Fukuoka 812-82, Japan

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 myelo-blastic leukemia patients in the future.

¹ This work was supported by Grants-in-Aid 08261211, 09250211, and 09255241 from the Ministry of Education, Science, Sports and Culture of Japan and by the Foundation for the Advancement of Clinical Medicine.

² To whom requests for reprints should be addressed. Phone: 81-92-642-5230; Fax: 81-92-642-5247.

Received 1/ 3/97. Accepted 6/18/97.

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