Increased expression of telomere length regulating factors TRF1, TRF2 and TIN2 in patients with adult T-cell leukemia.

Here, we report that freshly isolated unstimulated adult T-cell leukemia (ATL) cells present high telomerase activity compared to asymptomatic carriers or normal donors. In spite of this high telomerase activity, ATL cells retained shorter telomeres compared to those of uninfected cells isolated from the same patients. Because the safeguarding of telomere length is critical to the unlimited proliferation of tumor cells, we investigated the underlying mechanism for short telomere maintenance in ATL cells. Transcriptional and posttranscriptional expression of telomere-binding proteins TRF1, TRF2, TIN2 and POT1, known to regulate telomere homeostasis and protection, were evaluated. We found that TRF1 and TRF2 are overexpressed in in vivo patient's samples from ATL but not asymptomatic carriers, while levels of POT1 expression did not specifically increase in ATL. To gain insights into the regulation of TRF genes in HTLV-I infected cells, we investigated the expression of TIN2, a regulator of these genes, and found an increase in TIN2 expression in ATL patients. Together our results underscore the importance of telomerase and telomere length regulating factors as novel markers for ATL disease progression and as potential therapeutic targets for the treatment of HTLV-I-associated malignancies.