Monitoring therapy in canine malignant lymphoma and leukemia with serum thymidine kinase 1 activity - evaluation of a new, fully automated non-radiometric assay

Abstract

Abstract. Thymidine kinase 1 (TK), which is involved in the synthesis of DNA precursors, is only expressed in S-G2 cells. Serum TK levels correlate to the proliferative activity of tumor disease. Determinations of TK levels have so far relied on radio enzyme assay (REA) and experimental ELISA methods, which have limited the clinical use of this biomarker, although recent studies in dogs with malignant lymphoma (ML) demonstrate its wide potential. A non-radiometric method based on a competitive immunoassay with specific anti-3'-azido-deoxythymidine monophosphate (AZTMP) antibodies has been further developed into the fully automated Liaison TK assay (DiaSorin). Sera from healthy dogs (n=30), and dogs with leukemia (LEUK) (n=35), ML (n=84), nonhematological tumors (n=50), and inflammatory disease (n=14) were tested using both methods. Lymphoma and LEUK samples were available before and during chemotherapy. The coefficients of variation for the Liaison TK assay in this study were 6.3 and 3.4% (low/high TK, respectively), and the correlation between TK REA (X) and the Liaison TK assay (Y) was y=0.9203x + 1.3854 (R 2 =0.9501). The TK1 levels measured during chemotherapy gave very clear differences between dogs in complete remission and dogs out of remission.A Tukey-Kramer analysis showed that all LEUKs and MLs out of remission differed significantly from the other groups. The Liaison TK assay showed high precision, high sensitivity and a good correlation to the TK REA. The Liaison TK assay provides valuable clinical information in the treatment and management of canine LEUK and ML, with a potential to be further validated in human trials.

Adoptive T-cell therapy improves treatment of canine non–Hodgkin lymphoma post chemotherapy

“…Serum TK is a prognostic factor in several human cancers, including NHL and canine malignancies254647 and transient increases in serum TK levels occur after chemotherapy, surgery, inflammation, and infection48. We demonstrate that TK levels also correlated with in vitro propagation and in vivo persistence of infused T cells.…”

Concentration of Lipocalin Region of Collagen XXVII Alpha 1 in the Serum of Dogs with Hemangiosarcoma

“…While evidence for the validation of serum thymidine kinase (TK) activity as a screening tool for HSA is currently not available in the scientific literature, TK activity is used for diagnosis and monitoring of lymphoma and leukemia in humans and a similar use has been proposed for dogs. [11][12][13] In addition, multiparameter flow cytometry has been used to examine expression of cell-surface determinants associated with hematopoietic precursors that have potential for endothelial differentiation. 14 The results of this study indicate that quantitation of serum collagen XXVII peptide has potential utility as a diagnostic test for the detection of HSA in dogs.…”

Elevated serum thymidine kinase activity in canine splenic hemangiosarcoma*

“…Serum and plasma TK1 activity was evaluated by a commercial laboratory (Veterinary Diagnostics Institute, Simi Valley, CA, USA). The LIAISON (DiaSorin, Stillwater, MN, USA) TK assay is an indirect, modified two‐step, competitive chemiluminescence immunoassay (CLIA) for the quantitative determination of TK1 in serum and plasma, previously validated for use in canine samples 30 . The assay utilizes AZT as substrate and an isoluminol–AZTMP (3′‐azido‐3′‐deoxythymidine mono phosphate) conjugate 30 .…”