Authors: | Souza, L. M.; Boone, T. C.; Gabrilove, J.; Lai, P. H.; Zsebo, K. M.; Murdock, D. C.; Chazin, V. R.; Bruszewski, J.; Lu, H.; Chen, K. K.; Barendt, J.; Platzer, E.; Moore, M. A. S.; Mertelsmann, R.; Welte, K. |
Article Title: | Recombinant human granulocyte colony-stimulating factor: Effects on normal and leukemic myeloid cells |
Abstract: | Experiments were conducted to isolate and characterize the gene and gene product of a human hematopoietic colony-stimulating factor with pluripotent biological activities. This factor has the ability to induce differentiation of a murine myelomonocytic leukemia cell line WEHI-3B(D+) and cells from patients with newly diagnosed acute nonlymphocytic leukemia (ANLL). A complementary DNA copy of the gene encoding a pluripotent human granulocyte colony-stimulating factor (hG-CSF) was cloned and expressed in Escherichia. colt. The recombinant form of hG-CSF is capable of supporting neutrophil proliferation in a CFU-GM assay. In addition, recombinant hG-CSF can support early erythroid colonies and mixed colony formation. Competitive binding studies done with 125I-labeled hG-CSF and cell samples from two patients with newly diagnosed human leukemias as well as WEHI-3B(D+) cells showed that one of the human leukemias (ANLL, classified as M4) and the WEHI-3B(D+) cells have receptors for hG-CSF. Furthermore, the murine WEHI-3B(D+) cells and human leukemic cells classified as M2, M3, and M4 were induced by recombinant hG-CSF to undergo terminal differentiation to macrophages and granulocytes. The secreted form of the protein produced by the bladder carcinoma cell line 5637 was found to be O-glycosylated and to have a molecular weight of 19,600. |
Keywords: | leukemia; unclassified drug; drug efficacy; animals; mice; heredity; genes; cell line; cell differentiation; in vitro study; molecular cloning; dna; genetic engineering; leukemia, myeloid; escherichia coli; recombinant proteins; murinae; plasmids; bone marrow cell; radioisotope; colony-forming units assay; granulocyte colony stimulating factor; granulocyte colony-stimulating factor; adverse drug reaction; colony-stimulating factors; reticuloendothelial system; drug comparison; gene isolation; granulocytes; topical drug administration; humans; human; priority journal; article; nonlymphatic leukemia; blood and hemopoietic system; colony stimulating factor i 125 |
Journal Title: | Science |
Volume: | 232 |
Issue: | 4746 |
ISSN: | 0036-8075 |
Publisher: | American Association for the Advancement of Science |
Date Published: | 1986-04-04 |
Start Page: | 61 |
End Page: | 65 |
Language: | English |
DOI: | 10.1126/science.2420009 |
PUBMED: | 2420009 |
PROVIDER: | scopus |
DOI/URL: | |
Notes: | Article -- Export Date: 18 August 2021 -- Source: Scopus |