Recombinant human granulocyte colony-stimulating factor: effects on normal and leukemic myeloid cells.
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 coli. 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.
Souza
L M
LM
Boone
T C
TC
Gabrilove
J
J
Lai
P H
PH
Zsebo
K M
KM
Murdock
D C
DC
Chazin
V R
VR
Bruszewski
J
J
Lu
H
H
Chen
K K
KK
Barendt
J
J
Platzer
E
E
Moore
M A S
MAS
Mertelsmann
R
R
Welte
K
K
D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects; D002460:Cell Line; D003114:Colony-Forming Units Assay; D003115:Colony-Stimulating Factors / Q000235:genetics / Q000494:pharmacology*; D004247:DNA / Q000378:metabolism; D004926:Escherichia coli / Q000235:genetics; D005796:Genes; D016179:Granulocyte Colony-Stimulating Factor; D006098:Granulocytes / Q000502:physiology*; D006801:Humans; D007938:Leukemia / Q000473:pathology*; D007951:Leukemia, Myeloid / Q000473:pathology; D051379:Mice; D010957:Plasmids; D011994:Recombinant Proteins / Q000494:pharmacology*
D003115:Colony-Stimulating Factors; D011994:Recombinant Proteins; D016179:Granulocyte Colony-Stimulating Factor; D004247:DNA