Suppression of telomerase activity and cytokine messenger RNA levels in acute myelogenous leukemia cells in vivo in patients by amifostine and interleukin 4

High levels of telomerase activity and high rates of cell proliferation are associated with a poor prognosis in acute myelogenous leukemia. Furthermor e, cytokine production by leukemia cells is believed to play an important r ole in determining the proliferative characteristics of leukemia, The irt v ivo effects of two noncytotoxic agents on these parameters were determined in 33 acute myelogenous leukemia patients. Three daily doses of interleukin (IL) 4 or a single dose of amifostine reduced telomerase activity in the l eukemia marrow cells in 7 of 9 and 11 of 13 patients, respectively. The adm inistration of a single dose of amifostine resulted in a reduction in tumor necrosis factor alpha and IL-6 transcript levels in the marrow cells of 10 of 13 and 12 of 13 patients in which these transcripts were present. The a dministration of only three doses of IL-4 or a single dose of amifostine ha s a significant effect on leukemia cell parameters, which are believed to h ave a significant impact on the irt vivo biology of the disease and an its response to remission induction therapy.