Specific binding of radioiodinated human GM-CSF to the blast cells of acute myeloblastic leukemia.
We describe here the presence of two classes of binding sites for GM-CSF expressed on blasts freshly isolated from five AML patients and one patient with CML in blastic phase: one of high-affinity (38-177 per cell, KD 8-150 pM) and one of low-affinity (121-806 per cell, KD 503-2683 pM). No correlation is observed between the receptor number, receptor affinity, and the growth stimulatory effect of GM-CSF on leukemic blast progenitors. Blasts from two cases showed no or negligible response to GM-CSF but expressed comparable numbers of receptors when compared with the numbers expressed by the sensitive blasts. Our data suggest that significant proliferative effects of GM-CSF can occur at low levels of high-affinity receptor occupancy. Lack of responsiveness to GM-CSF in some AML patients is not correlated to the absence of GM-CSF receptors on leukemic cells. Reduction in the growth of blast progenitors at high concentrations of GM-CSF may be attributed to the differentiating activity of GM-CSF via low-affinity receptors on leukemic cells.
Murohashi
I
I
First Department of Internal Medicine, Tokyo Medical and Dental University, Japan.
Tohda
S
S
Suzuki
T
T
Nagata
K
K
Yamashita
Y
Y
Nara
N
N
D001667:Binding, Competitive; D002455:Cell Division; D003115:Colony-Stimulating Factors / Q000378:metabolism* / Q000494:pharmacology; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D006133:Growth Substances / Q000378:metabolism* / Q000494:pharmacology; D006801:Humans; D007377:Interleukin-3 / Q000494:pharmacology; D007457:Iodine Radioisotopes / Q000378:metabolism; D007700:Kinetics; D015470:Leukemia, Myeloid, Acute / Q000378:metabolism* / Q000473:pathology; D008747:Methylcellulose; D014411:Neoplastic Stem Cells / Q000378:metabolism* / Q000473:pathology; D011956:Receptors, Cell Surface / Q000032:analysis*; D016184:Receptors, Colony-Stimulating Factor; D011994:Recombinant Proteins / Q000494:pharmacology; D014407:Tumor Cells, Cultured / Q000473:pathology
D003115:Colony-Stimulating Factors; D006133:Growth Substances; D007377:Interleukin-3; D007457:Iodine Radioisotopes; D011956:Receptors, Cell Surface; D016184:Receptors, Colony-Stimulating Factor; D011994:Recombinant Proteins; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D008747:Methylcellulose