title: 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.
authors.affiliation: Department of Internal Medicine II, Faculty of Medicine, University Miyazaki, Kiyotake, Miyazaki, Japan. puyan@fc.miyazaki-u.ac.jp
authors.forename: Yoko
authors.initials: Y
authors.lastname: Kubuki
authors.forename: Muneou
authors.initials: M
authors.lastname: Suzuki
authors.forename: Hidenori
authors.initials: H
authors.lastname: Sasaki
authors.forename: Takanori
authors.initials: T
authors.lastname: Toyama
authors.forename: Kiyoshi
authors.initials: K
authors.lastname: Yamashita
authors.forename: Koichi
authors.initials: K
authors.lastname: Maeda
authors.forename: Akio
authors.initials: A
authors.lastname: Ido
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Matsuoka
authors.forename: Akihiko
authors.initials: A
authors.lastname: Okayama
authors.forename: Toshio
authors.initials: T
authors.lastname: Nakanishi
authors.forename: Hirohito
authors.initials: H
authors.lastname: Tsubouchi
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D005260:Female; D015490:HTLV-I Infections / Q000097:blood / Q000201:enzymology* / Q000235:genetics; D006801:Humans; D015459:Leukemia-Lymphoma, Adult T-Cell / Q000175:diagnosis / Q000201:enzymology* / Q000235:genetics; D007963:Leukocytes, Mononuclear / Q000737:chemistry / Q000201:enzymology; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D011446:Prospective Studies; D015183:Restriction Mapping; D012698:Serologic Tests; D016019:Survival Analysis; D019098:Telomerase / Q000235:genetics / Q000378:metabolism*; D016615:Telomere / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*
chemical_list: D019098:Telomerase