Impaired telomere regulation mechanism by TRF1 (telomere-binding protein),but not TRF2 expression, in acute leukemia cells

Telomere regulation is suggested to be an important mechanism in cellular p roliferation and cellular senescence not only in normal diploid cells but a lso in neoplastic cells, including human leukemia cells. We studied the pos sible correlation among telomere length, telomerase (a ribonuclear protein that synthesizes the telemeres de novo) activity, hTERT (a catalytic subuni t of telomerase) expression, and TRF1 and TRF2 (telomere DNA binding protei ns) expression in human acute leukemia cells. The hTERT expression level wa s strongly associated with telomerase activity (P = 0.0001), indicating tha t the expression level of the catalytic subunit (hTERT) regulates telomeras e activity in human acute leukemia cells. TRF1 expression, which is believe d to control telomere length, was significantly elevated in patients with a cute lymphoblastic leukemia (ALL) (P = 0.0232) compared to those in acute m yeloid leukemia (AML); TRF1 expression tended to be higher in patients with out telomere shortening (P = 0.077) and in those with hTERT expression (P = 0.055). This indicates that TRF1 may act to monitor telomere length under the condition of up-regulated telomerase activity in some neoplastic cells. In contrast, TRF2 expression in acute leukemia did not show any correlatio n with telomere parameters in this study. Although the precise regulation m echanism of telomere length is still uncertain, these results may suggest t hat regulation of telomere length is partially associated with TRF1 express ion, whereas dysfunction of TRF1 expression may be speculated in a subset o f acute leukemia.