Telomerase functions beyond telomere maintenance in primary cutaneous T-cell lymphoma.
Blood
; 123(12): 1850-9, 2014 Mar 20.
Article
en En
| MEDLINE
| ID: mdl-24470590
ABSTRACT
Telomere erosion may be counteracted by telomerase. Here we explored telomere length (TL) and telomerase activity (TA) in primary cutaneous T-cell lymphoma (CTCL) by using quantitative polymerase chain reaction and interphase quantitative fluorescence in situ hybridization assays. Samples from patients with Sézary syndrome (SS), transformed mycosis fungoides (T-MF), and cutaneous anaplastic large cell lymphoma were studied in parallel with corresponding cell lines to evaluate the relevance of TL and TA as target candidates for diagnostic and therapeutic purposes. Compared with controls, short telomeres were observed in aggressive CTCL subtypes such as SS and T-MF and were restricted to neoplastic cells in SS. While no genomic alteration of the hTERT (human telomerase catalytic subunit) locus was observed in patients' tumor cells, TA was detected. To understand the role of telomerase in CTCL, we manipulated its expression in CTCL cell lines. Telomerase inhibition rapidly impeded in vitro cell proliferation and led to cell death, while telomerase overexpression stimulated in vitro proliferation and clonogenicity properties and favored tumor development in immunodeficient mice. Our data indicate that, besides maintenance of TL, telomerase exerts additional functions in CTCL. Therefore, targeting these functions might represent an attractive therapeutic strategy, especially in aggressive CTCL.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Contexto en salud:
6_ODS3_enfermedades_notrasmisibles
Problema de salud:
6_lymphomas_multiple_myeloma
/
6_skin_diseases
Asunto principal:
Neoplasias Cutáneas
/
Linfoma Cutáneo de Células T
/
Telomerasa
/
Homeostasis del Telómero
Tipo de estudio:
Observational_studies
Límite:
Animals
/
Female
/
Humans
/
Male
Idioma:
En
Revista:
Blood
Año:
2014
Tipo del documento:
Article