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

Abstract

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.