title: Short telomeres and high telomerase activity in T-cell prolymphocytic leukemia.
abstract: To test the role of telomere biology in T-cell prolymphocytic leukemia (T-PLL), a rare aggressive disease characterized by the expansion of a T-cell clone derived from immuno-competent post-thymic T-lymphocytes, we analyzed telomere length and telomerase activity in subsets of peripheral blood leukocytes from 11 newly diagnosed or relapsed patients with sporadic T-PLL. Telomere length values of the leukemic T cells (mean+/-s.d.: 1.53+/-0.65 kb) were all below the 1st percentile of telomere length values observed in T cells from healthy age-matched controls whereas telomere length of normal T- and B cells fell between the 1st and 99th percentile of the normal distribution. Leukemic T cells exhibited high levels of telomerase and were sensitive to the telomerase inhibitor BIBR1532 at doses that showed no effect on normal, unstimulated T cells. Targeting the short telomeres and telomerase activity in T-PLL seems an attractive strategy for the future treatment of this devastating disease.
authors: Department of Hematology, University Hospital Essen, University of Duisburg-Essen, Essen, Germany. alexander.roeth@uni-due.de
authors: A
authors: A
authors: Röth
authors: J
authors: J
authors: Dürig
authors: H
authors: H
authors: Himmelreich
authors: S
authors: S
authors: Bug
authors: R
authors: R
authors: Siebert
authors: U
authors: U
authors: Dührsen
authors: P M
authors: PM
authors: Lansdorp
authors: G M
authors: GM
authors: Baerlocher
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D062365:Aminobenzoates / Q000494:pharmacology; D001402:B-Lymphocytes / Q000648:ultrastructure; D005260:Female; D006801:Humans; D015461:Leukemia, Prolymphocytic, T-Cell / Q000201:enzymology / Q000235:genetics* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009281:Naphthalenes / Q000494:pharmacology; D009363:Neoplasm Proteins / Q000032:analysis* / Q000037:antagonists & inhibitors; D013601:T-Lymphocytes / Q000648:ultrastructure; D019098:Telomerase / Q000032:analysis* / Q000037:antagonists & inhibitors; D016615:Telomere / Q000648:ultrastructure*
chemical_list: D062365:Aminobenzoates; C458523:BIBR 1532; D009281:Naphthalenes; D009363:Neoplasm Proteins; C509186:TERT protein, human; D019098:Telomerase