Correlation of telomerase activity with development and progression of adult T-cell leukemia

Telomerase is an enzyme that adds hexameric TTAGGG nucleotide repeats to th e ends of vertebrate chromosomal DNAs (i.e. telomeres) to compensate for lo sses that occur with each round of DNA replication. Telomerase activity, de monstrable in most human tumors, enables them to maintain telomere stabilit y. Peripheral blood mononuclear cells were sampled from 57 patients seropos itive for human T-lymphotropic virus type I (HTLV-I), including 24 asymptom atic viral carriers, ten smoldering type, five chronic type, and 18 acute t ype adult T-cell leukemia (ATL). Telomerase activity was determined in samp les using a modified telomeric repeat amplification protocol. We semiquanti tatively determined telomerase activity by serial dilution of each sample. All of 23 samples from acute and chronic type ATL patients were positive, s even of ten (70%) smoldering type patients and seven of 24 (29.2%) asymptom atic viral carriers were positive. Disease progression from asymptomatic vi ral carrier to acute type correlated with telomerase activity. Two samples from chronic type ATL patients with relatively high telomerase activity pro gressed to the acute type within 1 month. Serum lactate dehydrogenase level also correlated with telomerase activity. These results indicate that reac tivation of telomerase activity is a key event in development and progressi on of ATL, and telomerase could be a useful marker for predicting the cours e of disease. Accordingly, ATL could be a good candidate disease for trials of telomerase inhibitors, as novel anticancer drugs. (C) 1999 Elsevier Sci ence Ltd. All rights reserved.