Telomerase activity and telomere length as prognostic factors of adult T-cell leukemia

Abstract

For the oncogenesis of many malignancies, it is crucial to prevent the shortening of the telomeres by the action of telomerase. In this study, clinical data and disease outcomes were analyzed in conjunction with the telomerase activity (TA) and telomere length (TL) of peripheral blood mononuclear cells. The study was carried out in 22 patients with adult T-cell leukemia (ATL) (7 chronic and 15 acute types) and in 13 asymptomatic human T-lymphotropic virus type 1 (HTLV-1) carriers. The mean values of TA in acute and chronic type patients were 13.8 and 1.6 total product generated (TPG) units, respectively, as determined by telomeric repeat amplification assays. The mean TA values in HTLV-1 carriers and healthy volunteers were 1.8 and 0.7 TPG, respectively. The mean TA value in acute type patients was significantly higher than in the three other subject groups. The mean TL values in patients with acute and chronic types were 5.39 and 4.38 Kb, respectively, while the mean TL values in HTLV-1 carriers and healthy volunteers were 7.69 and 7.06 Kb, respectively. The mean TL values in all ATL patients and in non-ATL subjects were 5.2 and 7.3 Kb, respectively. The former value is significantly shorter than the latter (p < 0.01). Neither TA nor TL of ATL cells showed any significant association with the number of ATL cells, serum soluble interleukin-2 receptor, or serum lactate dehydrogenase in the peripheral blood of acute type patients. This suggests that the levels of TA and TL did not reflect the ATL tumor load. The median survival period of acute ATL patients with high TA and shortened TL was 0.47 years, however, which was significantly shorter than that of acute ATL patients with low TA and normal TL (4.21 years) (p < 0.002). These data suggest that high TA and shortened TL were associated with poorer prognosis, and that TA and TL may be novel markers for the prognosis of ATL patients.

Tumor Cell Development: A Role for Viruses and Telomerase Activity?

“…Furthermore, the median survival period of acute adult T-cell leukemia patients was reduced when comparing those with shortened telomeres and high telomerase activity with those with normal telomere length and low telomerase activity. 27 These results are in accordance with the notion that stabilization of short telomeres by telomerase is associated with (most likely as a cause of) cancer initiation and/or progression. There is also some evidence supporting direct binding of viral proteins into proteins of the telomere shelterin complex, thus inducing telomere dysfunction.…”

Pharmacogenomic Approach of Telomerase in Cancer: Importance of End Zone Variability

“…A study demonstrated that patients with multiple myeloma with high telomerase activity and short telomere length presented a poor prognosis (Wu, Orme et al 2003). Accordingly, another study reports the same results in adult T-cell leukemia, suggesting that telomerase www.intechopen.com activity and low telomere content may be novel markers for the prognosis of these diseases (Kubuki, Suzuki et al 2005).…”

Telomere dysfunction and its role in haematological cancer

“…Using TRF analysis, they showed that TL was decreased in this disease in comparison to normal controls. They also demonstrated that TA was increased and that the patients with increased TA had a poorer prognosis (Kubuki et al, 2005). A year later, Bellon et al (2006) reported that TL measured by Q-FISH was shortened in adult T-cell leukaemia/lymphoma.…”