Enhancement of drug cytotoxicity by recruitment of leukemic myeloblasts with humoral stimulation.

To demonstrate that the effect of 1-beta-D-arabinofuranosylcytosine can be increased when the leukemic cell growth fraction is augmented by induced humoral factors, bone marrow cells from 14 patients with acute myeloblastic leukemia were studied in vitro. Cells were cultured in either pooled stimulatory serum, obtained from leukemic patients undergoing chemotherapy, or autologous leukemic pre-treatment serum. After 2 days in culture, serum containing 1-beta-D-arabinofuranosylcytosine was added. Cells cultured in stimulatory serum proliferated markedly when compared with cells cultured in pretreatment serum, as measured by tritiated thymidine incorporation into an acid-insoluble precipitate, tritiated thymidine labeling indices, and viable tumor cell counts. The cytotoxic effect of 1-beta-D-arabinofuranosylcytosine was enhanced in those cells initially cultured in stimulatory serum relative to cells initially cultured in pretreatment serum. These studies are consistent with the hypothesis that induced humoral stimulation of acute myeloblastic leukemic cells in vitro recruits a greater tumor growth fraction and thereby increases the cytotoxicity of cycle-dependent drugs.