Document Detail


Telomerase activity and telomere length in patients with acute promyelocytic leukemia: indicative of proliferative activity, disease progression, and overall survival.
MedLine Citation:
PMID:  18567608     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
S H Ghaffari; N Shayan-Asl; A H Jamialahmadi; K Alimoghaddam; A Ghavamzadeh
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2008-06-20
Journal Detail:
Title:  Annals of oncology : official journal of the European Society for Medical Oncology / ESMO     Volume:  19     ISSN:  1569-8041     ISO Abbreviation:  Ann. Oncol.     Publication Date:  2008 Nov 
Date Detail:
Created Date:  2008-10-27     Completed Date:  2008-11-04     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9007735     Medline TA:  Ann Oncol     Country:  England    
Other Details:
Languages:  eng     Pagination:  1927-34     Citation Subset:  IM    
Affiliation:
Hematology, Oncology and BMT Research Center, Tehran University Medical Sciences, Tehran, Iran. shghaffari2000@yahoo.com
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MeSH Terms
Descriptor/Qualifier:
Adolescent
Adult
Antineoplastic Agents / therapeutic use
Arsenicals / therapeutic use
Cell Growth Processes / drug effects,  physiology
Disease Progression
Enzyme Activation / drug effects
Female
Humans
Leukemia, Promyelocytic, Acute / drug therapy,  enzymology*,  genetics*
Male
Middle Aged
Oncogene Proteins, Fusion / biosynthesis
Oxides / therapeutic use
Survival Rate
Telomerase / blood*
Telomere / drug effects,  metabolism*
Chemical
Reg. No./Substance:
0/Antineoplastic Agents; 0/Arsenicals; 0/Oncogene Proteins, Fusion; 0/Oxides; 0/promyelocytic leukemia-retinoic acid receptor alpha fusion oncoprotein; 1327-53-3/arsenic trioxide; EC 2.7.7.49/Telomerase

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