title: Telomerase expression in B-cell chronic lymphocytic leukemia predicts survival and delineates subgroups of patients with the same igVH mutation status and different outcome.
abstract: 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.
authors.affiliation: Section of Oncology, Department of Oncology and Surgical Sciences, University of Padua, Padua, Italy.
authors.forename: L
authors.initials: L
authors.lastname: Terrin
authors.forename: L
authors.initials: L
authors.lastname: Trentin
authors.forename: M
authors.initials: M
authors.lastname: Degan
authors.forename: I
authors.initials: I
authors.lastname: Corradini
authors.forename: R
authors.initials: R
authors.lastname: Bertorelle
authors.forename: P
authors.initials: P
authors.lastname: Carli
authors.forename: N
authors.initials: N
authors.lastname: Maschio
authors.forename: M D
authors.initials: MD
authors.lastname: Bo
authors.forename: F
authors.initials: F
authors.lastname: Noventa
authors.forename: V
authors.initials: V
authors.lastname: Gattei
authors.forename: G
authors.initials: G
authors.lastname: Semenzato
authors.forename: A
authors.initials: A
authors.lastname: De Rossi
mesh_terms: D051997:ADP-ribosyl Cyclase 1 / Q000032:analysis; D000328:Adult; D000368:Aged; D001402:B-Lymphocytes / Q000201:enzymology; D005260:Female; D006801:Humans; D007143:Immunoglobulin Heavy Chains / Q000235:genetics*; D007135:Immunoglobulin Variable Region / Q000235:genetics*; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000201:enzymology / Q000235:genetics* / Q000401:mortality; D008297:Male; D008875:Middle Aged; D009154:Mutation; D019098:Telomerase / Q000235:genetics*; D051746:ZAP-70 Protein-Tyrosine Kinase / Q000032:analysis
chemical_list: D007143:Immunoglobulin Heavy Chains; D007135:Immunoglobulin Variable Region; D051746:ZAP-70 Protein-Tyrosine Kinase; C509186:TERT protein, human; D019098:Telomerase; D051997:ADP-ribosyl Cyclase 1