title: Telomere length as a prognostic parameter in chronic lymphocytic leukemia with special reference to VH gene mutation status.
abstract: B-cell chronic lymphocytic leukemia (CLL) consists of 2 prognostic entities where cases with mutated immunoglobulin V(H) genes have better outcome than unmutated cases. V(H)-mutated CLLs display longer telomeres compared with unmutated cases and telomere length has been indicated to predict outcome, although the prognostic value of telomere length has not been fully established in CLL. We analyzed telomere length, V(H) gene mutation status, and clinical parameters in a large series of CLL. Telomere length was assessed by quantitative polymerase chain reaction (PCR), giving a very good correlation to telomere length estimated by Southern blotting (P < .001). The prognostic information given by mutation status (n = 282) and telomere length (n = 246) was significant (P < .001, respectively). Telomere length was a prognostic factor for stage A (P = .021) and stage B/C (P = .018) patients, whereas mutation status predicted outcome only in stage A patients (P < .001). Furthermore, mutated CLLs were subdivided by telomere length into 2 groups with different prognoses (P = .003), a subdivision not seen for unmutated cases (P = .232). Interestingly, the V(H)-mutated group with short telomeres had an overall survival close to that of the unmutated cases. Thus, by combining V(H) mutation status and telomere length, an improved subclassification of CLL was achieved identifying previously unrecognized patient groups with different outcomes.
authors.affiliation: Department of Medical Biosciences, Pathology, Umeå University, SE-90187 Umeå, Sweden.
authors.forename: Pawel
authors.initials: P
authors.lastname: Grabowski
authors.forename: Magnus
authors.initials: M
authors.lastname: Hultdin
authors.forename: Karin
authors.initials: K
authors.lastname: Karlsson
authors.forename: Gerard
authors.initials: G
authors.lastname: Tobin
authors.forename: Anna
authors.initials: A
authors.lastname: Aleskog
authors.forename: Ulf
authors.initials: U
authors.lastname: Thunberg
authors.forename: Anna
authors.initials: A
authors.lastname: Laurell
authors.forename: Christer
authors.initials: C
authors.lastname: Sundström
authors.forename: Richard
authors.initials: R
authors.lastname: Rosenquist
authors.forename: Göran
authors.initials: G
authors.lastname: Roos
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015139:Blotting, Southern; D005260:Female; D005803:Genes, Immunoglobulin; D006801:Humans; D007143:Immunoglobulin Heavy Chains / Q000235:genetics*; D016130:Immunophenotyping; D017404:In Situ Hybridization, Fluorescence; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000175:diagnosis* / Q000235:genetics*; D008198:Lymph Nodes / Q000473:pathology; D008297:Male; D008875:Middle Aged; D015233:Models, Statistical; D009154:Mutation; D016133:Polymerase Chain Reaction; D011379:Prognosis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D016615:Telomere / Q000648:ultrastructure*; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D007143:Immunoglobulin Heavy Chains