title: Serum thymidine kinase activity: analytical performance, age-related reference ranges and validation in chronic lymphocytic leukemia.
abstract: BACKGROUND
  To date no age-related reference ranges are available for serum thymidine kinase (TK1) activity. Being a proliferation marker, it may be used as a prognostic marker in malignant diseases, including chronic lymphocytic leukemia (CLL). Our aim was to establish age-specific reference ranges for TK1 and examine its utility as a screening marker in CLL, a disease of the elderly.
  
  
  METHODS
  Serum TK1 activity was measured by a competitive chemiluminescent immunoassay in 369 healthy adults and 115 de novo CLL patients.
  
  
  RESULTS
  We observed a statistically significant decline in TK1 activity from young (18-35 years) to middle-aged (36-60 years) and further on to elderly (60-86 years) healthy individuals. Age-related reference range was: <30 U/L for young, <25 U/L for middle-aged and <19 U/L for elderly. There was no difference in TK1 activity between the studied healthy men and women. In CLL patients, TK1 activity was the highest in the advanced Rai stages. The area under the receiver operating characteristic curve (ROC-AUC) for TK1 was 0.840 (95% CI: 0.787-0.892), for differentiating CLL patients from age and sex matched healthy controls, with a cut-off value of 10.5 U/L (sensitivity: 80.9%, specificity: 73.4%). TK1 was significantly elevated in CD38+/Zap70+ CLL patients, and showed significant correlation with WBC and absolute B-cell count.
  
  
  CONCLUSIONS
  In the healthy, serum TK1 activity does not differ in the two sexes but declines significantly with age. As such, use of age-related reference ranges is warranted, especially when evaluating CLL patients who generally belong to the elderly age group.
authors.affiliation: Department of Laboratory Medicine, Medical and Health Science Center, University of Debrecen, Debrecen, Hungary.
authors.forename: Eszter
authors.initials: E
authors.lastname: Szánthó
authors.affiliation: Department of Laboratory Medicine, Medical and Health Science Center, University of Debrecen, Debrecen, Hungary.
authors.forename: Harjit Pal
authors.initials: HP
authors.lastname: Bhattoa
authors.affiliation: Department of Laboratory Medicine, Medical and Health Science Center, University of Debrecen, Debrecen, Hungary.
authors.forename: Mária
authors.initials: M
authors.lastname: Csobán
authors.affiliation: Department of Laboratory Medicine, Medical and Health Science Center, University of Debrecen, Debrecen, Hungary.
authors.forename: Péter
authors.initials: P
authors.lastname: Antal-Szalmás
authors.affiliation: Department of Laboratory Medicine, Medical and Health Science Center, University of Debrecen, Debrecen, Hungary.
authors.forename: Anikó
authors.initials: A
authors.lastname: Újfalusi
authors.affiliation: Department of Laboratory Medicine, Medical and Health Science Center, University of Debrecen, Debrecen, Hungary.
authors.forename: János
authors.initials: J
authors.lastname: Kappelmayer
authors.affiliation: Department of Laboratory Medicine, Medical and Health Science Center, University of Debrecen, Debrecen, Hungary.
authors.forename: Zsuzsanna
authors.initials: Z
authors.lastname: Hevessy
mesh_terms: D051997:ADP-ribosyl Cyclase 1 / Q000378:metabolism; D000293:Adolescent; D000328:Adult; D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D001402:B-Lymphocytes / Q000166:cytology; D001774:Blood Chemical Analysis / Q000379:methods* / Q000592:standards*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007118:Immunoassay; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000097:blood* / Q000201:enzymology; D007958:Leukocyte Count; D008163:Luminescent Measurements; D008297:Male; D008875:Middle Aged; D012016:Reference Values; D015203:Reproducibility of Results; D013937:Thymidine Kinase / Q000097:blood*; D055815:Young Adult; D051746:ZAP-70 Protein-Tyrosine Kinase / Q000378:metabolism
chemical_list: D013937:Thymidine Kinase; D051746:ZAP-70 Protein-Tyrosine Kinase; C497261:ZAP70 protein, human; D051997:ADP-ribosyl Cyclase 1