Binding properties and proliferative effects of human recombinant granulocyte-macrophage colony-stimulating factor in primary leukemia and lymphoma.
Binding of radiolabeled human granulocyte-macrophage colony-stimulating factor (GM-CSF) was studied with blast cells from eight patients with acute myeloblastic leukemia (AML), and neoplastic lymphoid cells from one patient with acute lymphoblastic leukemia (ALL), two patients with chronic lymphocytic leukemia (CLL) and one patient with undiagnosed B cell neoplasia. In all AML cases studied, Scatchard graphs of the direct binding data were curvilinear, and were best fitted by curves derived from a two-binding-site model; one site with high affinity (Kd1 = 12-71 pM; 174-602 sites/cell) and the other with low affinity (Kd2 = 0.5-2.7 nM; 1137-6020 sites/cell). A cross-linking study on blast cells from one AML patient demonstrated specific bands which were similar to those reported for peripheral blood neutrophils. Furthermore, blast colony assays for the same preparations showed remarkable proliferative response to GM-CSF in the concentration range from 0.3 nM to 7.0 nM (ED50 greater than 0.7 nM). This concentration range is approximately one order of magnitude higher than that which is effective for colony formation from normal bone marrow progenitors (ED50 in equilibrium 0.1 nM). No significant correlation could be observed between the responsiveness of blast progenitors to GM-CSF, and the numbers or affinities of GM-CSF binding sites demonstrated on blast cells. In studies with neoplastic lymphoid cells from four patients, 125I-GM-CSF also specifically bound in two cases, while response to GM-CSF was not observed in these cases. These results indicate that the expression of GM-CSF receptor is not restricted to the GM-CSF-responsive AML blast cells, but can be observed in other AML blast cells and even in neoplastic lymphoid cells.
Piao
Y F
YF
Third Department of Internal Medicine, Faculty of Medicine, University of Tokyo.
Chiba
S
S
Tojo
A
A
Urabe
A
A
Nara
N
N
Miyazono
K
K
Takaku
F
F
D001665:Binding Sites; D002455:Cell Division / Q000187:drug effects; D003115:Colony-Stimulating Factors / Q000378:metabolism / Q000494:pharmacology*; D003432:Cross-Linking Reagents; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D006133:Growth Substances / Q000378:metabolism / Q000494:pharmacology*; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000378:metabolism*; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000378:metabolism*; D011956:Receptors, Cell Surface / Q000032:analysis*; D016184:Receptors, Colony-Stimulating Factor; D011994:Recombinant Proteins / Q000494:pharmacology; D013223:Statistics as Topic; D014407:Tumor Cells, Cultured / Q000187:drug effects
D003115:Colony-Stimulating Factors; D003432:Cross-Linking Reagents; D006133:Growth Substances; D011956:Receptors, Cell Surface; D016184:Receptors, Colony-Stimulating Factor; D011994:Recombinant Proteins; D016178:Granulocyte-Macrophage Colony-Stimulating Factor