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Annals of Oncology Advance Access originally published online on June 20, 2008
Annals of Oncology 2008 19(11):1927-1934; doi:10.1093/annonc/mdn394
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© The Author 2008. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. For permissions, please email: journals.permissions@oxfordjournals.org

hematologic malignancies

Telomerase activity and telomere length in patients with acute promyelocytic leukemia: indicative of proliferative activity, disease progression, and overall survival

S. H. Ghaffari*, N. Shayan-Asl, A. H. Jamialahmadi, K. Alimoghaddam and A. Ghavamzadeh

Hematology, Oncology and BMT Research Center, Tehran University Medical Sciences, Tehran, Iran

* Correspondence to: Dr Seyed H. Ghaffari, Assistant Professor, Hematology, Oncology and BMT Research Center, Tehran University Medical Sciences, Shariaty Hospital, Tehran, Iran. Tel: +98-21-84902665; Fax: +98-21-88004140; E-mail: shghaffari2000{at}yahoo.com

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.

Key words: acute promyelocytic leukemia, arsenic trioxide, NB4, telomerase activity, telomere length

Received for publication January 8, 2008. Accepted for publication May 21, 2008.


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