Effects of S-phase-specific agents on granulocyte-macrophage and erythroid progenitor cells obtained from normal individuals and from patients with chronic myelogenous leukemia.

The effects of three S-phase-specific agents, [3H]thymidine, hydroxyurea, and 1-beta-D-arabinofuranosylcytosine, on granulocyte-macrophage colony-forming units (CFU-C) and erythroid progenitor cells (erythroid burst-forming units) (BFU-E) from the bone marrow or peripheral blood obtained from 23 normal individuals and 12 patients with chronic myelogenous leukemia were investigated. CFU-C, regardless of their source, showed comparable degrees of sensitivity to each of the S-phase-specific agents, with perhaps a slightly greater level of sensitivity to [3H]thymidine. In contrast, the sensitivities of chronic myelogenous leukemia and normal marrow BFU-E to the 3 agents were quite different, with essentially all BFU-E being killed by [3H]thymidine, 50 to 70% being killed by 1-beta-D-arabinofuranosylcytosine, and only 15 to 20% being killed by hydroxyurea. BFU-E present in normal peripheral blood were insensitive to [3H]thymidine or hydroxyurea but were sensitive to 1-beta-D-arabinofuranosylcytosine. These studies demonstrated similarities between the CFU-C and BFU-E of CML patients and the CFU-C and BFU-E present in normal bone marrow. On the other hand, the sensitivities of normal peripheral blood progenitor cells to "S-phase-specific" agents differed from that of CML progenitor cells or the progenitor cells present in normal bone marrow. Additionally, these studies have demonstrated the limitations inherent in suicide techniques as methods for estimating the cell cycle characteristics of clonogenic cells.