HM Sassenfeld

Recombinant human granulocyte-macrophage (GM) colony-stimulating factor (GM-CSF), G-CSF, and interleukin-3 (IL-3) labeled with 125I were used to study the characteristics and distribution of receptors for these factors on in vitro cell lines and on cells from patients with acute nonlymphocytic leukemia (ANL) and acute lymphocytic leukemia (ALL). Receptors for GM-CSF and G-CSF were restricted to a subset of myelomonocytic cell lines whereas IL-3 receptors were also found on pre-B- or early B-cell lines. Receptors for all three CSFs were broadly distributed on ANL cells, with considerable variability in levels of expression. Measurement of the colony-forming ability of ANL cells in response to the CSFs showed that there was no direct correlation between the ability of the cells to respond to a growth factor and the absolute number of receptors expressed for that growth factor. Binding of radiolabeled IL-3 and GM-CSF to ANL cells produced complex biphasic curves. Further analysis showed that both IL-3 and GM-CSF were able to partially compete for specific binding of the heterologous radiolabeled ligand to cells from several ANL patients, suggesting that heterogeneity may exist in human CSF receptors. These results provide new insights into the complex role that CSFs may play in ANL.

Recombinant human granulocyte-macrophage (GM) colony-stimulating factor (GM-CSF), G-CSF, and interleukin-3 (IL-3) labeled with 125I were used to study the characteristics and distribution of receptors for these factors on in vitro cell lines and on cells from patients with acute nonlymphocytic leukemia (ANL) and acute lymphocytic leukemia (ALL). Receptors for GM-CSF and G-CSF were restricted to a subset of myelomonocytic cell lines whereas IL-3 receptors were also found on pre- B- or early B-cell lines. Receptors for all three CSFs were broadly distributed on ANL cells, with considerable variability in levels of expression. Measurement of the colony-forming ability of ANL cells in response to the CSFs showed that there was no direct correlation between the ability of the cells to respond to a growth factor and the absolute number of receptors expressed for that growth factor. Binding of radiolabeled IL-3 and GM-CSF to ANL cells produced complex biphasic curves. Further analysis showed that both IL-3 and GM-CSF were able to partially compete for specific binding of the heterologous radiolabeled ligand to cells from several ANL patients, suggesting that heterogeneity may exist in human CSF receptors. These results provide new insights into the complex role that CSFs may play in ANL.

In vivo administration of human recombinant granulocyte colony-stimulating factor (rG-CSF) was evaluated for effects on survival, hematologic recovery, and engraftment in an allogeneic murine bone marrow transplantation (BMT) model involving T-cell depletion. Post-BMT recipients of continuous subcutaneous infusions of rG-CSF (n = 62) for 14 days had a significant survival advantage compared with post-BMT controls (n = 60) that received phosphate-buffered saline (PBS) infusions. Moreover, recipients of rG-CSF had significantly increased numbers of circulating leukocytes on days 7 and 14 post-BMT. Engraftment was not adversely affected. Administration of rG-CSF after transplantation of T-cell-depleted histoincompatible bone marrow benefits survival and leukocyte recovery without compromising engraftment.

Abstract In vivo administration of human recombinant granulocyte colony- stimulating factor (rG-CSF) was evaluated for effects on survival, hematologic recovery, and engraftment in an allogeneic murine bone marrow transplantation (BMT) model involving T-cell depletion. Post-BMT recipients of continuous subcutaneous infusions of rG-CSF (n = 62) for 14 days had a significant survival advantage compared with post-BMT controls (n = 60) that received phosphate-buffered saline (PBS) infusions. Moreover, recipients of rG-CSF had significantly increased numbers of circulating leukocytes on days 7 and 14 post-BMT. Engraftment was not adversely affected. Administration of rG-CSF after transplantation of T-cell-depleted histoincompatible bone marrow benefits survival and leukocyte recovery without compromising engraftment.