TY - JOUR
T1 - Telomerase expression in B-cell chronic lymphocytic leukemia predicts survival and delineates subgroups of patients with the same igVH mutation status and different outcome
AU - Terrin, L.
AU - Trentin, L.
AU - Degan, M.
AU - Corradini, I.
AU - Bertorelle, R.
AU - Carli, P.
AU - Maschio, N.
AU - Bo, M. D.
AU - Noventa, F.
AU - Gattei, V.
AU - Semenzato, G.
AU - De Rossi, A.
PY - 2007/5
Y1 - 2007/5
N2 - Activation of telomerase reverse transcriptase (hTERT) is essential for unlimited cell growth and plays a critical role in tumorigenesis. We investigated hTERT gene expression in 134 B-cell chronic lymphocytic leukemia (B-CLL) cases and evaluated its prognostic value with other prognostic markers (IgVH mutation status, CD38 and ZAP-70 expression). Real-time PCR assays to quantify either all hTERT transcripts (AT) or only the full length (FL) transcript encoding the functional protein were developed. hTERT-AT levels strongly correlated with hTERT-FT levels (r = 0.743, P <0.0001); both inversely correlated with the percentage of IgVH mutation (P <0.005) and were significantly higher in unmutated than in mutated cases (P = 0.004 and P = 0.001, respectively). The hTERT values which best discriminated between the unmutated and mutated IgVH cases were 150 and 40 copies for hTERT-AT and hTERT-FL, respectively. Using these cut-off values, there was a significant difference in the survival of patients with high or low hTERT levels (P <0.0001). Unmutated cases with low hTERT levels had an overall survival close to mutated cases with high hTERT levels. Thus, this work identifies hTERT-RNA level as a new prognostic marker in B-CLL, and may be used to identify previously unrecognized patient groups with the same IgVH mutation status and different disease outcomes.
AB - Activation of telomerase reverse transcriptase (hTERT) is essential for unlimited cell growth and plays a critical role in tumorigenesis. We investigated hTERT gene expression in 134 B-cell chronic lymphocytic leukemia (B-CLL) cases and evaluated its prognostic value with other prognostic markers (IgVH mutation status, CD38 and ZAP-70 expression). Real-time PCR assays to quantify either all hTERT transcripts (AT) or only the full length (FL) transcript encoding the functional protein were developed. hTERT-AT levels strongly correlated with hTERT-FT levels (r = 0.743, P <0.0001); both inversely correlated with the percentage of IgVH mutation (P <0.005) and were significantly higher in unmutated than in mutated cases (P = 0.004 and P = 0.001, respectively). The hTERT values which best discriminated between the unmutated and mutated IgVH cases were 150 and 40 copies for hTERT-AT and hTERT-FL, respectively. Using these cut-off values, there was a significant difference in the survival of patients with high or low hTERT levels (P <0.0001). Unmutated cases with low hTERT levels had an overall survival close to mutated cases with high hTERT levels. Thus, this work identifies hTERT-RNA level as a new prognostic marker in B-CLL, and may be used to identify previously unrecognized patient groups with the same IgVH mutation status and different disease outcomes.
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U2 - 10.1038/sj.leu.2404607
DO - 10.1038/sj.leu.2404607
M3 - Article
C2 - 17344921
AN - SCOPUS:34247622889
VL - 21
SP - 965
EP - 972
JO - Leukemia
JF - Leukemia
SN - 0887-6924
IS - 5
ER -