BACKGROUND: The progressive shortening of telomeres and the activation of telomerase have been considered to be one of the key mechanisms in cellular immortalization and tumor progression. PATIENTS AND METHODS: About 300 sequential samples were collected from 40 patients during the course of acute promyelocytic leukemia (APL) disease. Telomerase activity (TA) and terminal restriction fragment (TRF) length were assessed by TRAP and Southern blot analyses, respectively. PML-retinoic acid receptor alpha (RARa)/glucose-6-phosphate dehydrogenase transcripts were quantified by real-time PCR. RESULTS: About 90% of the patients had a significant reduction in telomere length (TL) relative to the control (median 3.5 versus 11.37 kbp; P < 0.001). A significant positive correlation between TL and PML-RARa expression was found (P = 0.001). Telomerase was activated in all patients; however, TA level was significantly higher in the group of relapsed patients than patient with newly diagnosed. The group of patients with shortened TRF and elevated TA had a significantly poorer overall survival. CONCLUSIONS: The shortened TL and elevated TA in APL patients are mainly indicative of extensive proliferative activity and they correlate with disease progression and relapse; thus, they may serve as prognostic factors for a subset of APL patients with more aggressive disease and poor outcome, those who may not respond favorably to arsenic therapy.
BACKGROUND: The progressive shortening of telomeres and the activation of telomerase have been considered to be one of the key mechanisms in cellular immortalization and tumor progression. PATIENTS AND METHODS: About 300 sequential samples were collected from 40 patients during the course of acute promyelocytic leukemia (APL) disease. Telomerase activity (TA) and terminal restriction fragment (TRF) length were assessed by TRAP and Southern blot analyses, respectively. PML-retinoic acid receptor alpha (RARa)/glucose-6-phosphate dehydrogenase transcripts were quantified by real-time PCR. RESULTS: About 90% of the patients had a significant reduction in telomere length (TL) relative to the control (median 3.5 versus 11.37 kbp; P < 0.001). A significant positive correlation between TL and PML-RARa expression was found (P = 0.001). Telomerase was activated in all patients; however, TA level was significantly higher in the group of relapsed patients than patient with newly diagnosed. The group of patients with shortened TRF and elevated TA had a significantly poorer overall survival. CONCLUSIONS: The shortened TL and elevated TA in APLpatients are mainly indicative of extensive proliferative activity and they correlate with disease progression and relapse; thus, they may serve as prognostic factors for a subset of APLpatients with more aggressive disease and poor outcome, those who may not respond favorably to arsenic therapy.
Authors: Muhamed Baljevic; Bogdan Dumitriu; Ju-Whei Lee; Elisabeth M Paietta; Peter H Wiernik; Janis Racevskis; Christina Chen; Eytan M Stein; Robert E Gallagher; Jacob M Rowe; Frederick R Appelbaum; Bayard L Powell; Richard A Larson; Steven E Coutré; Jeffrey Lancet; Mark R Litzow; Selina M Luger; Neal S Young; Martin S Tallman Journal: Acta Haematol Date: 2016-09-16 Impact factor: 2.195
Authors: Martin S Tallman; Haesook T Kim; Pau Montesinos; Frederick R Appelbaum; Javier de la Serna; John M Bennett; Guillermo Deben; Clara D Bloomfield; Jose Gonzalez; James H Feusner; Marcos Gonzalez; Robert Gallagher; Jose D Gonzalez-San Miguel; Richard A Larson; Gustavo Milone; Elisabeth Paietta; Chelo Rayon; Jacob M Rowe; Concha Rivas; Charles A Schiffer; Edo Vellenga; Lois Shepherd; James L Slack; Peter H Wiernik; Cheryl L Willman; Miguel A Sanz Journal: Blood Date: 2010-09-21 Impact factor: 22.113
Authors: Linda E Carlson; Erin L Zelinski; Michael Speca; Lynda G Balneaves; Jennifer M Jones; Daniel Santa Mina; Peter M Wayne; Tavis S Campbell; Janine Giese-Davis; Peter Faris; Jennifer Zwicker; Kamala Patel; Tara L Beattie; Steve Cole; Kirsti Toivonen; Jill Nation; Philip Peng; Bruce Thong; Raimond Wong; Sunita Vohra Journal: Contemp Clin Trials Date: 2017-05-30 Impact factor: 2.226