Heat Sensitivity, Thermotolerance, and Profile of Heat Shock Protein Synthesis of Human Myelogenous Leukemias

In anticipation of using single or fractionated hyperthermia treatment in ex vivo purging of leukemic bone marrow in the clinic, we have compared the hyperthermic sensitivity, kinetics of thermotolerance, and heat-shock protein synthesis in three human myelogenous leukemic cell lines. In terms of heat sensitivity, the chronic myelogenous leukemic cell line K562 was found to be the most resistant. The D_e s of the 43, 44, and 45°C heat survival curves were 22, 13, and 6 min, respectively. HL-60 and KG-1, both acute myelogenous leukemic lines, however, were found to be several fold more sensitive to the cytotoxic effects of heat. The D_e s of the 43, 44, and 45°C heat survival curves for HL-60 were 7.6, 5.6, and 2 min and for KG-1 were 5.7, 4.5, and 1.7 min, respectively. All cell lines developed thermotolerance. However, K562 developed more tolerance which lasted for longer times. For K562 cells at priming heat doses of 45°C/10 min, 42°C/2 h, or 41°C/2 h thermotolerance was maximum at 4 to 6 h and began to decay at 24 h. HL-60 and KG-1 cells showed some thermotolerance at the priming doses of 45°C/5 min or 42°C/30 min and had fully decayed by 24 h. K562 cells synthesized M_r70,000 heat shock protein for over 24 h following the 45°C/10 min heat shock, while HL-60 and KG-1 synthesized M_r70,000 heat shock protein for 2–4 h for the same amount of cell kill. These studies suggest that most human leukemias may be extremely sensitive to the cytotoxic effects of heat, and in vitro purging of leukemias from bone marrow specimens by heat needs to be further studied both by in vitro and in vivo model systems.