Serum thymidine kinase activity: analytical performance, age-related reference ranges and validation in chronic lymphocytic leukemia

PLoS One. 2014 Mar 12;9(3):e91647. doi: 10.1371/journal.pone.0091647. eCollection 2014.

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.

Conclusion: 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • ADP-ribosyl Cyclase 1 / metabolism
  • Adolescent
  • Adult
  • Age Factors
  • Aged
  • Aged, 80 and over
  • B-Lymphocytes / cytology
  • Blood Chemical Analysis / methods*
  • Blood Chemical Analysis / standards*
  • Female
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Immunoassay
  • Leukemia, Lymphocytic, Chronic, B-Cell / blood*
  • Leukemia, Lymphocytic, Chronic, B-Cell / enzymology
  • Leukocyte Count
  • Luminescent Measurements
  • Male
  • Middle Aged
  • Reference Values
  • Reproducibility of Results
  • Thymidine Kinase / blood*
  • Young Adult
  • ZAP-70 Protein-Tyrosine Kinase / metabolism

Substances

  • Thymidine Kinase
  • ZAP-70 Protein-Tyrosine Kinase
  • ZAP70 protein, human
  • ADP-ribosyl Cyclase 1

Grants and funding

The work is supported by the TÁMOP-4.2.2.A-11/1/KONV-2012-0025 project. The project is co-financed by the European Union and the European Social Fund. This work is supported by the OTKA 105073 research grant (HPB) and by the National Office for Research and Technology (presently National Development Agency) of Hungary (TECH-09-A1-2009-0113; mAB-CHIC) (PAS). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.