title: Telomeres and prognosis in patients with chronic lymphocytic leukaemia.
abstract: In the present study, telomere length, telomerase activity, the mutation load of immunoglobulin variable heavy chain (IGHV) genes, and established prognostic factors were investigated in 78 patients with chronic lymphocytic leukaemia (CLL) to determine the impact of telomere biology on the pathogenesis of CLL. Telomere length was measured by an automated multi-colour flow-FISH, and an age-independent delta telomere length (ΔTL) was calculated. CLL with unmutated IGHV genes was associated with shorter telomeres (p = 0.002). Furthermore, we observed a linear correlation between the frequency of IGHV gene mutations and elongation of telomeres (r = 0.509, p < 0.001). With respect to prognosis, a threshold ΔTL of -4.2 kb was the best predictor for progression-free and overall survival. ΔTL was not significantly altered over time or with therapy. The correlation between the mutational load in IGHV genes and the ΔTL in CLL might reflect the initial telomere length of the putative cell of origin (pre- versus post-germinal center B cells). In conclusion, the ΔTL is a reliable prognostic marker for patients with CLL. Short telomeres and high telomerase activity as occurs in some patients with CLL with a worse prognosis might be an ideal target for treatment with telomerase inhibitors.
authors.affiliation: Department of Haematology, University of Duisburg Essen, Essen, Germany. ludger.sellmann@uk-essen.de
authors.forename: Ludger
authors.initials: L
authors.lastname: Sellmann
authors.forename: Dirk
authors.initials: D
authors.lastname: de Beer
authors.forename: Marius
authors.initials: M
authors.lastname: Bartels
authors.forename: Bertram
authors.initials: B
authors.lastname: Opalka
authors.forename: Holger
authors.initials: H
authors.lastname: Nückel
authors.forename: Ulrich
authors.initials: U
authors.lastname: Dührsen
authors.forename: Jan
authors.initials: J
authors.lastname: Dürig
authors.forename: Marc
authors.initials: M
authors.lastname: Seifert
authors.forename: Dörte
authors.initials: D
authors.lastname: Siemer
authors.forename: Ralf
authors.initials: R
authors.lastname: Küppers
authors.forename: Gabriela M
authors.initials: GM
authors.lastname: Baerlocher
authors.forename: Alexander
authors.initials: A
authors.lastname: Röth
mesh_terms: D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D007143:Immunoglobulin Heavy Chains / Q000235:genetics*; D007135:Immunoglobulin Variable Region / Q000235:genetics*; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000235:genetics* / Q000378:metabolism / Q000401:mortality* / Q000473:pathology / Q000628:therapy; D008297:Male; D009154:Mutation; D012189:Retrospective Studies; D015996:Survival Rate; D016615:Telomere / Q000235:genetics*
chemical_list: D007143:Immunoglobulin Heavy Chains; D007135:Immunoglobulin Variable Region