Telomerase expression in B-cell chronic lymphocytic leukemia predicts survival and delineates subgroups of patients with the same igVH mutation status and different outcome

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.