Telomerase, the ribonucleoprotein enzyme maintaining the telomeres of eukaryotic 
chromosomes, is up-regulated in the vast majority of human neoplasias but not in 
normal somatic tissues. Therefore, the telomerase complex represents a promising 
universal therapeutic target in cancer. Telomeric G-rich single-stranded DNA can 
adopt in vitro an intramolecular quadruplex structure, which has been shown to 
inhibit telomerase activity. We examined G-quadruplex interactive agent, 
telomestatin (SOT-095), for its ability to inhibit the proliferation of human 
leukemia cells, including freshly obtained leukemia cells. Telomere length was 
determined by either the terminal restriction fragment method or flow-FISH, and 
apoptosis was assessed by flow cytometry. Moreover, chemosensitivity was 
examined in telomestatin-treated U937 cells before ultimate telomere shortening. 
Treatment with telomestatin reproducibly inhibited telomerase activity in U937 
and NB4 cells followed by telomere shortening. Enhanced chemosensitivity toward 
daunorubicin and cytosine-arabinoside was observed in telomestatin-treated U937 
cells, before ultimate telomere shortening. Telomere shortening associated with 
apoptosis by telomestatin was evident in some freshly obtained leukemia cells 
from acute myeloid leukemia patients, regardless of sub-types of AML and 
post-myelodysplasia AML. These results suggest that disruption of telomere 
maintenance by telomestatin limits the cellular lifespan of AML cells, as well. 
However, in a minority of AML patients apoptosis was not evident, thus 
indicating that resistant mechanism might exist in some freshly obtained AML 
cells. Therefore, further investigation of telomestatin as a therapeutic agent 
is warranted.