Purging of acute myeloid leukemic cells by ether lipids and hyperthermia.
Ether lipids (EL) and hyperthermia have been shown to possess a relatively selective cytotoxicity to leukemic cells. In this study, the combined effects of EL (ET-18-OCH3, ET-16-NHCOCH3, or BM 41.440) and hyperthermia on the growth of hematopoietic progenitors, myeloid leukemic cell lines, and leukemic cells obtained from patients with acute myeloid leukemia (AML) were examined to determine if this combination resulted in a greater selective killing of leukemic cells than that achieved by either EL or heat alone. When the cells were treated simultaneously with EL (50 micrograms/mL) and hyperthermia (42 degrees C) for one hour, the killing of leukemic cell line cells was enhanced considerably. Among the three EL, however, the combination of ET-18-OCH3 and heat seemed to be the most cytotoxic to leukemic cell line cells with no effect on the growth of hematopoietic progenitors. An increase in the duration of treatment with ET-18-OCH3 to four hours with heat added during the last hour resulted in a further reduction of leukemic cell line cells while sparing 50% of hematopoietic progenitors after cryopreservation. The combined treatment with ET-18-OCH3 and heat also inhibited the growth of leukemic progenitors obtained from AML patients by 97% to 100%. These data indicate that the combined treatment with EL and hyperthermia might offer an efficient means to eliminate myeloid leukemic cells in vitro.
D001854:Bone Marrow Cells; D016026:Bone Marrow Transplantation; D002470:Cell Survival / Q000187:drug effects; D003114:Colony-Forming Units Assay; D006410:Hematopoiesis / Q000187:drug effects; D006412:Hematopoietic Stem Cells / Q000187:drug effects; D006801:Humans; D006979:Hyperthermia, Induced; D015470:Leukemia, Myeloid, Acute / Q000628:therapy*; D010742:Phospholipid Ethers / Q000494:pharmacology / Q000627:therapeutic use*; D014182:Transplantation, Autologous; D014407:Tumor Cells, Cultured / Q000187:drug effects
D010742:Phospholipid Ethers; C043297:ilmofosine