Primary human myeloid leukemia cells: comparative responsiveness to proliferative stimulation by GM-CSF or G-CSF and membrane expression of CSF receptors.
In vitro clonal culture of leukemic cells from patients with acute myeloid leukemia (AML) showed that cells from all subtypes tested could be stimulated to proliferate clonally either by purified recombinant human granulocyte-macrophage colony stimulating factor (GM-CSF) or by human cross-reactive, purified murine granulocyte CSF (G-CSF). The responsiveness of AML populations to CSF stimulation was quantitatively variable but was within the heterogeneous range exhibited by normal granulocyte-monocyte progenitor cells. A general concordance was noted between the proliferative effects of GM-CSF and G-CSF on the individual leukemic populations. All AML populations tested specifically bound 125I-labeled murine G-CSF; the level of labeling varied widely and correlated with AML subtype. Labeling levels on individual labeled leukemic cells were within the heterogeneous range exhibited by normal cells, but significant numbers of blast cells in M2, M4, and M5 AMLs appeared to lack membrane receptors for G-CSF. The level of labeling with G-CSF did not correlate with the frequency of clonogenic cells able to be stimulated by G-CSF. The data emphasized that GM-CSF and G-CSF are equivalent proliferative stimuli for human myeloid leukemia cells. Further, despite the potential ability of G-CSF to suppress murine leukemic cells, many AML blast cells lack significant numbers of G-CSF receptors. These considerations warrant caution in future attempts to use G-CSF in the therapy of acute myeloid leukemia.
D001853:Bone Marrow / Q000473:pathology; D002455:Cell Division / Q000187:drug effects; D003115:Colony-Stimulating Factors / Q000378:metabolism / Q000494:pharmacology*; D016179:Granulocyte Colony-Stimulating Factor; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D006133:Growth Substances / Q000378:metabolism / Q000494:pharmacology*; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000378:metabolism* / Q000473:pathology; D011956:Receptors, Cell Surface / Q000502:physiology*; D016184:Receptors, Colony-Stimulating Factor; D011994:Recombinant Proteins / Q000378:metabolism; D014407:Tumor Cells, Cultured
D003115:Colony-Stimulating Factors; D006133:Growth Substances; D011956:Receptors, Cell Surface; D016184:Receptors, Colony-Stimulating Factor; D011994:Recombinant Proteins; D016179:Granulocyte Colony-Stimulating Factor; D016178:Granulocyte-Macrophage Colony-Stimulating Factor