Cell cycle status of erythroid (BFU-E) progenitor cells from the bone marrows of patients on a clinical trial with purified recombinant human granulocyte-macrophage colony-stimulating factor.
Human Granulocyte-Macrophage Colony Stimulating Factor (GM-CSF) is active in vitro as a Burst Promoting Activity (BPA) for human erythroid (BFU-E) progenitor cells. In order to evaluate the effectiveness of GM-CSF as a proliferation-inducing stimulus for BFU-E in vivo, bone marrow cells from patients on a phase I/II clinical trial with recombinant human (rh) GM-CSF, were assessed in vitro for effects on the cycling status of BFU-E. Prior to treatment, BFU-E from marrows of the majority of these patients were in a slowly cycling state. Administration of rhGM-CSF to the patients enhanced BFU-E proliferation, and cessation of treatment with rhGM-CSF resulted in BFU-E returning to a slowly cycling state. Similar results were noted for CFU-GM. This study demonstrates that rhGM-CSF has proliferation-inducing activity for BFU-E in vivo, substantiating the in vitro BPA activity previously noted for GM-CSF, although it is not possible from the present studies in vivo to determine if this effect on BFU-E is directly or indirectly mediated.
Broxmeyer
H E
HE
Department of Medicine, Indiana University School of Medicine, Indianapolis 46223.
Cooper
S
S
Vadhan-Raj
S
S
D001853:Bone Marrow / Q000187:drug effects; D001854:Bone Marrow Cells; D002453:Cell Cycle / Q000187:drug effects; D003115:Colony-Stimulating Factors / Q000627:therapeutic use*; D004341:Drug Evaluation; D004920:Erythropoiesis / Q000187:drug effects; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D006133:Growth Substances / Q000627:therapeutic use*; D006412:Hematopoietic Stem Cells / Q000187:drug effects*; D006801:Humans; D011994:Recombinant Proteins / Q000627:therapeutic use
D003115:Colony-Stimulating Factors; D006133:Growth Substances; D011994:Recombinant Proteins; D016178:Granulocyte-Macrophage Colony-Stimulating Factor