title: Short telomere length is associated with NOTCH1/SF3B1/TP53 aberrations and poor outcome in newly diagnosed chronic lymphocytic leukemia patients.
abstract: Most previous studies on telomere length (TL) in chronic lymphocytic leukemia (CLL) are based on referral cohorts including a high proportion of aggressive cases. Here, the impact of TL was analyzed in a population-based cohort of newly diagnosed CLL (n = 265) and in relation to other prognostic markers. Short telomeres were particularly associated with high-risk genetic markers, such as NOTCH1, SF3B1, or TP53 aberrations, and predicted a short time to treatment (TTT) and overall survival (OS) (both P < 0.0001). TL was an independent prognostic factor and subdivided patients with otherwise good-prognostic features (e.g., mutated IGHV genes, favorable cytogenetics) into subgroups with different outcome. Furthermore, in follow-up samples (n = 119) taken 5-8 years after diagnosis, TL correlated well with TL at diagnosis and remained unaffected by treatment. Altogether, these novel data indicate that short TL already at diagnosis is associated with poor outcome in CLL and that TL can be measured at later stages of the disease.
authors.affiliation: Department of Immunology, Genetics, and Pathology, Rudbeck Laboratory, Uppsala University, Uppsala, Sweden.
authors.forename: Larry
authors.initials: L
authors.lastname: Mansouri
authors.forename: Pawel
authors.initials: P
authors.lastname: Grabowski
authors.forename: Sofie
authors.initials: S
authors.lastname: Degerman
authors.forename: Ulrika
authors.initials: U
authors.lastname: Svenson
authors.forename: Rebeqa
authors.initials: R
authors.lastname: Gunnarsson
authors.forename: Nicola
authors.initials: N
authors.lastname: Cahill
authors.forename: Karin Ekström
authors.initials: KE
authors.lastname: Smedby
authors.forename: Christian
authors.initials: C
authors.lastname: Geisler
authors.forename: Gunnar
authors.initials: G
authors.lastname: Juliusson
authors.forename: Göran
authors.initials: G
authors.lastname: Roos
authors.forename: Richard
authors.initials: R
authors.lastname: Rosenquist
mesh_terms: D000368:Aged; D014408:Biomarkers, Tumor / Q000235:genetics* / Q000378:metabolism; D018572:Disease-Free Survival; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000175:diagnosis / Q000235:genetics / Q000401:mortality / Q000628:therapy; D008297:Male; D008875:Middle Aged; D009154:Mutation; D010750:Phosphoproteins / Q000235:genetics* / Q000378:metabolism; D011237:Predictive Value of Tests; D000072260:RNA Splicing Factors; D051881:Receptor, Notch1 / Q000235:genetics* / Q000378:metabolism; D012189:Retrospective Studies; D017413:Ribonucleoprotein, U2 Small Nuclear / Q000235:genetics* / Q000378:metabolism; D015996:Survival Rate; D016615:Telomere / Q000235:genetics* / Q000378:metabolism; D016159:Tumor Suppressor Protein p53 / Q000235:genetics* / Q000378:metabolism
chemical_list: D014408:Biomarkers, Tumor; C497761:NOTCH1 protein, human; D010750:Phosphoproteins; D000072260:RNA Splicing Factors; D051881:Receptor, Notch1; D017413:Ribonucleoprotein, U2 Small Nuclear; C112491:SF3B1 protein, human; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53