HTLV-1 positive and negative T cells cloned from infected individuals display telomerase and telomere genes deregulation that predominate in activated but untransformed CD4+ T cells.
Zane, Linda; Sibon, David; CAPRARO, Valérieet al.
2012 • In International Journal of Cancer, 131 (4), p. 821-33
[en] Untransformed HTLV-1 positive CD4(+) cells from infected individuals are selected for expressing tax and displaying morphological features consistent with telomere dysfunctions. We show that in resting HTLV-1 positive CD4(+) cells cloned from patients, hTERT expression parallels tax expression and cell cycling. Upon activation, these cells dramatically augment tax expression, whereas their increase in telomerase activity is about 20 times lower than that of their uninfected counterpart. Activated HTLV-1 positive CD4(+) but not uninfected CD4(+) or CD8(+) clones also repress the transcription of TRF1, TPP1, TANK1, POT1, DNA-PKc and Ku80. Both infected and uninfected lymphocytes from infected individuals shared common telomere gene deregulations toward a pattern consistent with premature senescence. ATLL cells displayed the highest telomerase activity (TA) whereas recovered a telomere gene transcriptome close to that of normal CD4(+) cells. In conclusion HTLV-1-dependent telomere modulations seem involved in clonal expansion, immunosuppression, tumor initiation and progression.
Disciplines :
Genetics & genetic processes
Author, co-author :
Zane, Linda
Sibon, David
CAPRARO, Valérie ; Centre Hospitalier Universitaire de Liège - CHU > Secteur biologie moléculaire
Galia, Perrine
Karam, Maroun
Delfau-Larue, Marie-Helene
Gilson, Eric
Gessain, Antoine
Gout, Olivier
Hermine, Olivier
Mortreux, Franck
Wattel, Eric
Language :
English
Title :
HTLV-1 positive and negative T cells cloned from infected individuals display telomerase and telomere genes deregulation that predominate in activated but untransformed CD4+ T cells.
Publication date :
2012
Journal title :
International Journal of Cancer
ISSN :
0020-7136
eISSN :
1097-0215
Publisher :
John Wiley & Sons, Hoboken, United States - New York
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