Elimination of leukemic cells by the combined use of ether lipids in vitro

Two ether lipids, CP-46,665-1 (4-aminomethyl-1-[2,3-(di-n-decyloxy)-n- propyl]-4-phenylpiperidine) and ET-18-OCH3 (racemic 1-O-octadecyl-2-O-methylglycero-3-phosphocholine) have been shown to possess antileukemic activity in vitro. To explore the possible use of these compounds for purging remission bone marrow cells of leukemic cells, we examined the cytotoxic effect of these compounds on normal hematopoietic progenitor cells and leukemic cell line cells (HL-60, K-562, KG-1a, KG-1, and Daudi) by using the clonogenic assay. When cells were treated with CP-46,665-1 or ET-18-OCH3 (50 micrograms/ml for 1 h), these compounds did not inhibit the growth of normal progenitors, whereas the growth of the clonogenic leukemic cells was inhibited with differences in their sensitivities to the cytotoxic effect of CP-46,665-1 and ET-18-OCH3. Incubation of leukemic cells (HL-60 and Daudi cells) with both CP-46,665-1 (50 micrograms/ml) and ET-18-OCH3 (50 micrograms/ml) for 1 h resulted in a greater reduction of clonogenic leukemic cells than treated with each compound alone. Approximately a 3 log killing of clonogenic HL-60 cells and a 5 log killing of Daudi cells was achieved; however, the combined treatment of normal bone marrow cells with CP-46,665-1 and ET-18-OCH3 did not alter the growth of normal progenitors. This combined treatment also selectively eliminated the leukemic cells (HL-60 and Daudi cells) from a mixture (1000:1) of normal bone marrow cells and leukemic cells. It is conceivable that the pronounced difference in sensitivity to this combined treatment can be exploited for the elimination of residual leukemic cells in autologous remission marrow grafts.