Serum Thymidine Kinase Activity: Analytical Performance, Age-Related Reference Ranges and Validation in Chronic Lymphocytic Leukemia

Szánthó, Eszter; Bhattoa, Harjit Pal; Csobán, Mária; Antal‐Szalmás, Péter; Újfalusi, Anikó; Kappelmayer, János; Hevessy, Zsuzsanna

doi:10.1371/journal.pone.0091647

Cited by 11 publications

(6 citation statements)

References 42 publications

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“…There was no significant difference in the median TK1 protein levels between three different age groups (young, middle-aged and older). These results are in contrast to those of a previously published study which found that TK1 enzyme activity in healthy individuals decreased significantly with age [21]. Furthermore, TK1 protein determinations using a dot blot assay have shown a similar pattern, with serum TK1 protein concentrations increasing up to the age of 40 years and then decreasing with age [22].…”

Section: Correlations With Other Blood Parameterscontrasting

confidence: 99%

Arocell Tk 210 Elisa for Determination of Tk1 Protein: Age-Related Reference Ranges and Comparison with Other Tk1 Assays

Jagarlamudi¹,

Holmgren

Levedahl

et al. 2020

BioTechniques

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Thymidine kinase 1 (TK1) is an enzyme involved in DNA precursor synthesis that has been used as a biomarker for prognosis and monitoring of different malignancies. In this study, we compared two immunoassays for measuring TK1 protein concentrations: the TK 210 ELISA (AroCell AB) and TK1 ELISA from Abcam. Overall, the TK 210 ELISA showed higher sensitivity than the Abcam TK1 ELISA for differentiating hematological malignancies (sensitivity of 0.77 vs 0.45) as well as for distinguishing sera of patients with solid tumors from those of apparently healthy individuals (0.61 vs 0.20). There was no significant difference in the TK1 protein levels determined with the TK 210 ELISA between different age groups from apparently healthy individuals. These results strongly indicate that the AroCell TK 210 ELISA is accurate and sensitive enough to be a valuable tool in cancer management.

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Section: Correlations With Other Blood Parameterscontrasting

confidence: 99%

Arocell Tk 210 Elisa for Determination of Tk1 Protein: Age-Related Reference Ranges and Comparison with Other Tk1 Assays

Jagarlamudi¹,

Holmgren

Levedahl

et al. 2020

BioTechniques

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“…The standardization of chemiluminescence immunoassay for the assessment of serum thymidine kinase-1 (TK) levels significantly facilitated the introduction of this marker into clinical practice,100 and age-related normal reference values were recently defined and validated 101. When this test was included among diagnostic workup within prospective trials, raised TK levels (i.e.…”

Section: Resultsmentioning

confidence: 99%

“Identifying High-Risk Chronic Lymphocytic Leukemia: A Pathogenesis-Oriented Appraisal of Prognostic and Predictive Factors in Patients Treated With Chemotherapy With or Without Immunotherapy.”

Martinelli

Cuneo

Rigolin

2016

Mediterr J Hematol Infect Dis

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Chronic lymphocytic leukemia (CLL) displays an extremely variable clinical behaviour. Accurate prognostication and prediction of response to treatment are important in an era of effective first-line regimens and novel molecules for high risk patients. Because a plethora of prognostic biomarkers were identified, but few of them were validated by multivariable analysis in comprehensive prospective studies, we applied in this survey stringent criteria to select papers from the literature in order to identify the most reproducible prognostic/predictive markers. Each biomarker was analysed in terms of reproducibility across the different studies with respect to its impact on time to first treatment (TTFT), progression free survival (PFS), overall survival (OS) and response to treatment. We were able to identify the following biomarkers as the most reliable in guiding risk stratification in the daily clinical practice: 17p-/TP53 mutations, IGHV unmutated configuration, short telomeres and 11q-. However, the method for measuring telomere length was not validated yet and 11q- was predictive of inferior OS only in those patients who did not receive FCR-like combinations. Stage and lymphocytosis were predictive of shorter TTFT and age, high serum thymidine kinase levels and poor performance status were predictive of shorter OS. Using our criteria no parameter was found to independently predict for inferior response to treatment.

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“…Because of this characteristic, TK1 has been used as a proliferation marker in lymphomas and leukemias in human medicine for many years [10–12]. Several commercial assays are available to measure the TK1 activity levels in different malignancies, such as e.g., TK-REA, TK-Liaison, and Divitum [10, 29, 30]. Even though TK1 activity levels show a correlation with the stage of breast cancer disease, the overall sensitivity of the assays is rather low i.e., less than 35 % [30–32].…”

Section: Discussionmentioning

confidence: 99%

A clinical evaluation of the TK 210 ELISA in sera from breast cancer patients demonstrates high sensitivity and specificity in all stages of disease

Kumar

Aronsson²,

Pilko

et al. 2016

Tumor Biol.

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Thymidine kinase (TK1) is an enzyme involved in DNA synthesis that leaks into the blood as a result of high cell turnover, particularly in the case of cancer. Serum TK1 activity has been used for prognosis and monitoring of leukemia and lymphoma patients for many years. Here, we describe the first clinical results with the newly developed TK 210 ELISA from AroCell AB. Sera from 124 breast cancer patients with known TNM classification along with sera from 53 healthy females were analyzed by TK 210 ELISA for TK1 protein and TK1 activity levels by the 3[H]-deoxythymidine (dThd) phosphorylation assay. The limit of detection for the TK 210 ELISA was 0.17 ng/ml, and 60 % of the sera from female blood donors were below this value. The median TK1 levels found in sera from breast cancer patients with T1 to T4 stage disease were 0.31, 0.46, 0.47, and 0.55 ng/ml, and these levels significantly differed from healthy controls. The median values of the biomarker CA 15-3 were also increased in patient sera from T1 to T4 patients (16, 34, 36, 40 U/ml, respectively). TK 210 ELISA showed significantly higher sensitivity for the T1 and T2 breast cancer patients compared to the TK activity assay. The combination of the TK1 ELISA and CA 15-3 biomarkers demonstrated a significant increase in sensitivity up to 15 % compared to each marker alone. This evaluation of the TK 210 ELISA strongly suggests that it can provide independent and complementary information for patients with breast cancer.Electronic supplementary materialThe online version of this article (doi:10.1007/s13277-016-5024-z) contains supplementary material, which is available to authorized users.

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Serum Thymidine Kinase Activity: Analytical Performance, Age-Related Reference Ranges and Validation in Chronic Lymphocytic Leukemia

Cited by 11 publications

References 42 publications

Arocell Tk 210 Elisa for Determination of Tk1 Protein: Age-Related Reference Ranges and Comparison with Other Tk1 Assays

Arocell Tk 210 Elisa for Determination of Tk1 Protein: Age-Related Reference Ranges and Comparison with Other Tk1 Assays

“Identifying High-Risk Chronic Lymphocytic Leukemia: A Pathogenesis-Oriented Appraisal of Prognostic and Predictive Factors in Patients Treated With Chemotherapy With or Without Immunotherapy.”

A clinical evaluation of the TK 210 ELISA in sera from breast cancer patients demonstrates high sensitivity and specificity in all stages of disease

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