Receptor binding of human granulocyte colony-stimulating factor to the blast cells of myeloid leukemia.
Human granulocyte colony-stimulating factor (G-CSF) rapidly loses the biological activity and the receptor binding capacity following radioiodination. We have made a mutein of human G-CSF, KW-2228, in which Thr-1, Leu-3, Gly-4, Pro-5, and Cys-17 were respectively substituted with Ala, Thr, Tyr, Arg, and Ser; showed more potent G-CSF activity; and retained full biological activity and receptor binding capacity at least 2 weeks of radioiodination. G-CSF is an effective growth factor for the blasts of myeloid leukemia. Radioiodinated KW-2228 was prepared using solid-phase glucose oxidase-lactoperoxidase. Human leukemia cell lines and the blast cells from leukemia patients were examined for binding. High affinity binding sites were identified on myeloid cell lines and on the blasts obtained from acute myeloid leukemia patients. Scatchard analysis showed that a single binding site for G-CSF was observed (361-1688 receptors/cell; Kd 128-1400 pM). In contrast, specific binding of 125I-KW-2228 was not demonstrated on lymphoblastic cell lines or the blast cells of acute lymphoid leukemia or lymphoma. This difference was reflected in the effectiveness of G-CSF to stimulate colony formation in acute myeloid leukemia blasts, while G-CSF did not stimulate colony formation of the blast cells from acute lymphoid leukemia.
Department of Internal Medicine, Faculty of Medicine, University of Tokyo, Japan.
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YF
Piao
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Okabe
D001752:Blast Crisis / Q000378:metabolism*; D002460:Cell Line; D003115:Colony-Stimulating Factors / Q000235:genetics / Q000378:metabolism*; D004926:Escherichia coli / Q000235:genetics; D016179:Granulocyte Colony-Stimulating Factor; D006801:Humans; D007700:Kinetics; D007938:Leukemia; D015470:Leukemia, Myeloid, Acute / Q000378:metabolism / Q000473:pathology*; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000378:metabolism / Q000473:pathology*; D011956:Receptors, Cell Surface / Q000378:metabolism*; D016188:Receptors, Granulocyte Colony-Stimulating Factor; D011994:Recombinant Proteins / Q000378:metabolism
D003115:Colony-Stimulating Factors; D011956:Receptors, Cell Surface; D016188:Receptors, Granulocyte Colony-Stimulating Factor; D011994:Recombinant Proteins; D016179:Granulocyte Colony-Stimulating Factor