Abstract
BackgroundTo 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.MethodsSerum TK1 activity was measured by a competitive chemiluminescent immunoassay in 369 healthy adults and 115 de novo CLL patients.ResultsWe 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.ConclusionIn 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.
Highlights
Distinguishing from a few tumor specific biomarkers (PSA, AFP, HCG etc) [1,2,3], thymidine kinase 1 (TK1, ATP; thymidine 59phosphotransferase; EC.2.7.1.21) is one of the non-specific tumor markers that can be measured in continuously dividing cells [4]
TK has been reported as a prognostic marker in chronic lymphocytic leukemia (CLL) and in non-Hodgkin’s lymphoma [14,15,16,17]
Results of 115 CLL patients on presentation were compared with an equal number of age- and sex-matched controls (n = 115)
Summary
Distinguishing from a few tumor specific biomarkers (PSA, AFP, HCG etc) [1,2,3], thymidine kinase 1 (TK1, ATP; thymidine 59phosphotransferase; EC.2.7.1.21) is one of the non-specific tumor markers that can be measured in continuously dividing cells [4]. TK1 is a key cellular enzyme in the so-called salvage pathway of DNA synthesis. TK has been reported as a prognostic marker in chronic lymphocytic leukemia (CLL) and in non-Hodgkin’s lymphoma [14,15,16,17]. Konoplev et al showed that high serum TK1 levels predict poorer overall survival and higher risk of developing large B-cell lymphoma (Richter syndrome) [16]. The first TK measurement method was a radio-enzymatic assay using 125I-deoxyuridine [25]; later a non-radiometric, competitive, enzyme-linked, immunosorbent assay (ELISA) was developed [26]. To date no age-related reference ranges are available for serum thymidine kinase (TK1) activity. 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
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