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

Abstract

Telomere regulation is suggested to be an important mechanism in cellular proliferation and cellular senescence not only in normal diploid cells but also in neoplastic cells, including human leukemia cells. We studied the possible correlation among telomere length, telomerase (a ribonuclear protein that synthesizes the telemeres de novo) activity, hTERT (a catalytic subunit of telomerase) expression, and TRF1 and TRF2 (telomere DNA binding proteins) expression in human acute leukemia cells. The hTERT expression level was strongly associated with telomerase activity (P=0.0001), indicating that the expression level of the catalytic subunit (hTERT) regulates telomerase activity in human acute leukemia cells. TRF1 expression, which is believed to control telomere length, was significantly elevated in patients with acute lymphoblastic leukemia (ALL) (P=0.0232) compared to those in acute myeloid leukemia (AML); TRF1 expression tended to be higher in patients without 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 correlation with telomere parameters in this study. Although the precise regulation mechanism of telomere length is still uncertain, these results may suggest that regulation of telomere length is partially associated with TRF1 expression, whereas dysfunction of TRF1 expression may be speculated in a subset of acute leukemia.