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. Furthermore, cytokine production by leukemia cells is believed to play an important role in determining the proliferative characteristics of leukemia. The in vivo 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 leukemia marrow cells in 7 of 9 and 11 of 13 patients, respectively. The administration 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 administration of only three doses of IL-4 or a single dose of amifostine has a significant effect on leukemia cell parameters, which are believed to have a significant impact on the in vivo biology of the disease and on its response to remission induction therapy.
Preisler
H D
HD
Department of Medicine, Rush Cancer Institute, Chicago, Illinois 60612, USA.
Li
B
B
Yang
B L
BL
Huang
R W
RW
Devemy
E
E
Venugopal
P
P
Tao
M
M
Chopra
H
H
Gregory
S A
SA
Adler
S
S
Sivaraman
S
S
Toofanfard
P
P
Jajeh
A
A
Galvez
A
A
Robin
E
E
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D004999:Amifostine / Q000627:therapeutic use*; D001854:Bone Marrow Cells / Q000166:cytology / Q000187:drug effects / Q000201:enzymology; D016207:Cytokines / Q000235:genetics*; D005260:Female; D006801:Humans; D007375:Interleukin-1 / Q000235:genetics; D015847:Interleukin-4 / Q000627:therapeutic use*; D004915:Leukemia, Erythroblastic, Acute / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D015470:Leukemia, Myeloid, Acute / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D015479:Leukemia, Myelomonocytic, Acute / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D008297:Male; D008875:Middle Aged; D011518:Proto-Oncogene Proteins / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics* / Q000378:metabolism; D020794:Receptor Protein-Tyrosine Kinases / Q000235:genetics; D019098:Telomerase / Q000187:drug effects* / Q000378:metabolism; D014158:Transcription, Genetic; D016896:Treatment Outcome; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics; D051941:fms-Like Tyrosine Kinase 3
D016207:Cytokines; D007375:Interleukin-1; D011518:Proto-Oncogene Proteins; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D015847:Interleukin-4; C497970:FLT3 protein, human; D020794:Receptor Protein-Tyrosine Kinases; D051941:fms-Like Tyrosine Kinase 3; D019098:Telomerase; D004999:Amifostine