Reference : Telomere deregulations possess cytogenetic, phenotype, and prognostic specificities in a...
Scientific journals : Article
Life sciences : Genetics & genetic processes
Life sciences : Genetics & genetic processes
http://hdl.handle.net/2268/110202
Telomere deregulations possess cytogenetic, phenotype, and prognostic specificities in acute leukemias.
English
CAPRARO, Valérie mailto [Centre Hospitalier Universitaire de Liège - CHU > > Secteur biologie moléculaire]
Zane, Linda [> > > >]
Poncet, Delphine [> > > >]
Perol, David [> > > >]
Galia, Perrine [> > > >]
Preudhomme, Claude [> > > >]
Bonnefoy-Berard, Nathalie [> > > >]
Gilson, Eric [> > > >]
Thomas, Xavier [> > > >]
El-Hamri, Mohamed [> > > >]
Chelghoun, Youcef [> > > >]
Michallet, Mauricette [> > > >]
Wattel, Eric [> > > >]
Mortreux, Franck [> > > >]
Sibon, David [> > > >]
2011
Experimental Hematology
Elsevier Science
39
2
195-202.e2
Yes
International
0301-472X
Amsterdam
The Netherlands
[en] Antineoplastic Agents/therapeutic use ; Gene Expression Regulation, Neoplastic ; Humans ; Leukemia, Myeloid, Acute/drug therapy/genetics/physiopathology ; Phenotype ; Precursor Cell Lymphoblastic Leukemia-Lymphoma/drug therapy/genetics/physiopathology ; Prognosis ; Survival Analysis ; Telomerase/metabolism ; Telomere/genetics/metabolism ; Tumor Cells, Cultured ; Tumor Markers, Biological/metabolism
[en] OBJECTIVE: Telomeres are protected by tightly regulated factors and elongated by telomerase. Short and/or deprotected chromosomes are recombinogenic and thereby cancer prone. MATERIALS AND METHODS: Together with the quantification of telomerase activity (TA), measuring telomere length (TL) and expression of the genes that govern telomere protection and elongation are useful for assessing telomere homeostasis. RESULTS: By these means we demonstrate that TL, hTERT, and TA are in the order acute myelogenous leukemia (AML) > T-cell acute lymphoblastic leukemia (T-ALL) > B-cell acute lymphoblastic leukemia (B-ALL) > T-ALL > AML, and B-ALL > AML > T-ALL. AML0 and AML3 display the lowest amounts of hTERT transcripts, and ALL and AML cells with cytogenetic abnormalities possess the shortest telomeres. hTERT expression includes phenotype-specific RNA maturation and correlates with TA but not with TL. A wide ratio of TA to hTERT expression between leukemia subtypes suggests phenotype-specific hTERT post-transcriptional deregulations. B- and T-ALL overexpress Ku70 and Pinx1, T-ALL PTOP and RAP1, and B-ALL TRF2, the expression of which is significantly higher in cases with abnormal karyotype. hTERT transcription and TL correlate with response to intensive chemotherapy, and hTERT and RAD50 are independent prognostic factors for survival. CONCLUSIONS: Each leukemia subtype possesses specific telomere dysregulations that rely on phenotype, karyotype, response to treatment, and survival.
http://hdl.handle.net/2268/110202
also: http://hdl.handle.net/2268/170431
10.1016/j.exphem.2010.10.008
Copyright (c) 2011 Published by Elsevier Inc.

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