Telomerase activity and telomere length in patients with acute promyelocytic leukemia: indicative of proliferative activity, disease progression, and overall survival
| Autor: | Seyed H. Ghaffari, A. Ghavamzadeh, Kamran Alimoghaddam, N. Shayan-Asl, A.H. Jamialahmadi |
|---|---|
| Rok vydání: | 2008 |
| Předmět: |
Acute promyelocytic leukemia
Adult Male Telomerase Adolescent Oncogene Proteins Fusion Antineoplastic Agents Cell Growth Processes Arsenicals chemistry.chemical_compound Arsenic Trioxide Leukemia Promyelocytic Acute medicine Humans Arsenic trioxide Survival rate business.industry Cancer Oxides Hematology Middle Aged Telomere medicine.disease Enzyme Activation Survival Rate Leukemia Oncology chemistry Tumor progression Immunology Cancer research Disease Progression Female business |
| Zdroj: | Annals of oncology : official journal of the European Society for Medical Oncology. 19(11) |
| ISSN: | 1569-8041 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|