title: Telomere length and telomerase levels delineate subgroups of B-cell chronic lymphocytic leukemia with different biological characteristics and clinical outcomes.
abstract: BACKGROUND
  B-cell chronic lymphocytic leukemia is a clinically heterogeneous disease; some patients rapidly progress and die within a few years of diagnosis, whereas others have a long life expectancy with minimal or no treatment. Telomere length and telomerase levels have been proposed as prognostic factors; however, very few cases have been characterized for both parameters and no study has analyzed the prognostic value of the telomere/telomerase profile.
  
  
  METHODS
  One hundred and seventy-three cases of chronic lymphocytic leukemia were characterized for telomere lengths and telomerase levels by real-time polymerase chain reaction. Data were correlated with established prognostic markers, IGVH mutational status and chromosomal aberrations, and clinical outcome.
  
  
  RESULTS
  Telomere lengths were inversely correlated with telomerase levels (r(s) = -0.213; P = 0.012), and most of the cases of chronic lymphocytic leukemia with high levels (above median) of telomerase had short (below median) telomeres (P = 0.0001). Telomerase levels were higher and telomeres were shorter in unmutated IGVH cases than in mutated IGVH ones (P<0.0001). Chronic lymphocytic leukemias with 11q, 17p deletion or 12 trisomy had significantly higher levels of telomerase and shorter telomeres than those with no chromosomal aberration or the sole 13q deletion (P < 0.001). Telomere length/telomerase level profiles identified subgroups of patients with different clinical outcomes (P < 0.0001), even within the subsets of chronic lymphocytic leukemia defined by IGVH mutational status or chromosomal aberrations. Short telomere/high telomerase profile was independently associated with more rapid disease progression.
  
  
  CONCLUSIONS
  Comprehensive analyses of telomeres, telomerase, chromosomal aberrations, and IGVH mutational status delineate groups of chronic lymphocytic leukemias with distinct biological characteristics and clinical outcomes. The telomere/telomerase profile may be particularly useful in refining the prognosis of chronic lymphocytic leukemia patients with mutated IGVH and no high-risk chromosomal aberrations.
authors.affiliation: Department of Oncology and Surgical Sciences, Oncology Section, University of Padova,Padova, Italy.
authors.forename: Enrica
authors.initials: E
authors.lastname: Rampazzo
authors.forename: Laura
authors.initials: L
authors.lastname: Bonaldi
authors.forename: Livio
authors.initials: L
authors.lastname: Trentin
authors.forename: Carlo
authors.initials: C
authors.lastname: Visco
authors.forename: Sonia
authors.initials: S
authors.lastname: Keppel
authors.forename: Silvia
authors.initials: S
authors.lastname: Giunco
authors.forename: Federica
authors.initials: F
authors.lastname: Frezzato
authors.forename: Monica
authors.initials: M
authors.lastname: Facco
authors.forename: Elisabetta
authors.initials: E
authors.lastname: Novella
authors.forename: Ilaria
authors.initials: I
authors.lastname: Giaretta
authors.forename: Paola
authors.initials: P
authors.lastname: Del Bianco
authors.forename: Gianpietro
authors.initials: G
authors.lastname: Semenzato
authors.forename: Anita
authors.initials: A
authors.lastname: De Rossi
mesh_terms: D051997:ADP-ribosyl Cyclase 1 / Q000378:metabolism; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002869:Chromosome Aberrations; D005260:Female; D006801:Humans; D007143:Immunoglobulin Heavy Chains / Q000235:genetics; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000145:classification / Q000235:genetics* / Q000378:metabolism* / Q000401:mortality; D008297:Male; D008875:Middle Aged; D009154:Mutation; D011379:Prognosis; D016019:Survival Analysis; D019098:Telomerase / Q000235:genetics / Q000378:metabolism*; D059505:Telomere Homeostasis; D014158:Transcription, Genetic; D051746:ZAP-70 Protein-Tyrosine Kinase / Q000378:metabolism
chemical_list: D007143:Immunoglobulin Heavy Chains; D051746:ZAP-70 Protein-Tyrosine Kinase; D019098:Telomerase; D051997:ADP-ribosyl Cyclase 1