Telomerase functions beyond telomere maintenance in primary cutaneous T-cell lymphoma.
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.
Histologie et Pathologie Moléculaire des Tumeurs, University Bordeaux, Bordeaux, France; and.
Edith
E
Chevret
Laetitia
L
Andrique
Martina
M
Prochazkova-Carlotti
Jacky
J
Ferrer
David
D
Cappellen
Elodie
E
Laharanne
Yamina
Y
Idrissi
Anna
A
Boettiger
Wafa
W
Sahraoui
Florian
F
Ruiz
Anne
A
Pham-Ledard
Beatrice
B
Vergier
Francis
F
Belloc
Pierre
P
Dubus
Marie
M
Beylot-Barry
Jean-Philippe
JP
Merlio
D000818:Animals; D016022:Case-Control Studies; D016923:Cell Death; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D005260:Female; D064593:Heterografts; D006801:Humans; D017728:Lymphoma, Large-Cell, Anaplastic / Q000201:enzymology / Q000235:genetics; D016410:Lymphoma, T-Cell, Cutaneous / Q000201:enzymology* / Q000235:genetics / Q000473:pathology; D008297:Male; D051379:Mice; D016513:Mice, SCID; D009182:Mycosis Fungoides / Q000201:enzymology / Q000235:genetics; D009368:Neoplasm Transplantation; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012334:RNA, Neoplasm / Q000235:genetics / Q000378:metabolism; D012751:Sezary Syndrome / Q000201:enzymology / Q000235:genetics; D012878:Skin Neoplasms / Q000201:enzymology* / Q000235:genetics / Q000473:pathology; D019098:Telomerase / Q000037:antagonists & inhibitors / Q000235:genetics / Q000502:physiology*; D059505:Telomere Homeostasis / Q000235:genetics / Q000502:physiology*
D012333:RNA, Messenger; D012334:RNA, Neoplasm; D019098:Telomerase