4-Hydroperoxycyclophosphamide inhibits proliferation by human granulocyte-macrophage colony-forming cells (GM-CFC) but spares more primitive progenitor cells

Leuk Res. 1985;9(8):1017-21. doi: 10.1016/0145-2126(85)90072-4.

Abstract

Despite its considerable toxicity to haemopoietic colony-forming cells, 4-hydroperoxycyclophosphamide (4-HC) has successfully been used to purge marrow of leukaemic cells before it is used to rescue patients from high-dose chemoradiotherapy. These conflicting observations indicate that haemopoietic progenitor cells that are not detected by the established colony-forming assays survive exposure to 4-HC and repopulate the marrow. The recent finding that murine spleen colony-forming cells (CFU-S) are resistant to 4-HC [Porcellini A, et al. (1983) Expl Hemat. 11 (suppl 14) 331 (abstract)] [14] also indicates that sensitivity to 4-HC can be used to distinguish primitive progenitor cells from committed progenitor cells. As part of a study on the nature of a population of blast colony-forming cells in human bone marrow, we tested their sensitivity to 4-HC to see whether they also are spared by the drug. We found that 4-HC had much less effect on the blast colony-forming cells than on the granulocyte-macrophage colony-forming cells (GM-CFC). This result suggests that the blast-colony-forming cells may be early human haemopoietic progenitor cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anemia, Aplastic / therapy
  • Bone Marrow Cells
  • Cell Differentiation / drug effects
  • Cell Division / drug effects
  • Cell Survival
  • Colony-Forming Units Assay
  • Cyclophosphamide / analogs & derivatives*
  • Cyclophosphamide / pharmacology
  • Drug Resistance
  • Granulocytes / cytology*
  • Hematopoietic Stem Cells / cytology
  • Hematopoietic Stem Cells / drug effects*
  • Humans
  • Leukemia / therapy
  • Macrophages / cytology*
  • Transplantation, Autologous

Substances

  • Cyclophosphamide
  • perfosfamide