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Serum TK levels in CLL identify Binet stage A patients within biologically defined prognostic subgroups most likely to undergo disease progression

Matthews, Christine and Catherwood, Mark A. and Morris, T. C. and Kettle, Paul J. and Drake, Mary B. and Gilmore, William S. and Alexander, H. Denis (2006) Serum TK levels in CLL identify Binet stage A patients within biologically defined prognostic subgroups most likely to undergo disease progression. European Journal Of Haematology, 77 (4). pp. 309-317. ISSN 1600-0609

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Abstract

Objective: Serum thymidine kinase (TK) levels have been shown to be correlated with survival in many malignancies, including chronic lymphocytic leukaemia (CLL). This study was designed to investigate associations between TK levels and other prognostic markers, in newly and previously diagnosed Binet stage A patients. Furthermore, the use of serum TK measurement to identify subcategories of disease within those defined by IgVH mutational status, gene usage and chromosomal aberrations was investigated. Methods: Ninety-one CLL patients were enrolled. Serum TK levels were measured using a radioenzyme assay. IgVH mutational status and VH gene usage were determined using BIOMED-2 primers and protocol. Recurring chromosomal abnormalities were detected by interphase fluorescent in situ hybridisation (FISH). Flow cytometry and reverse transcriptase polymerase chain reaction (RT-PCR) determined CD38 and Zap-70 expression, respectively. Results: Significantly higher serum TK levels were found in IgVH unmutated, compared with IgVH mutated, patients (P < 0.001). Elevated TK levels were also found in patients with CD38 and Zap-70 positivity (P = 0.004, P < 0.001, respectively), short lymphocyte doubling time (LDT) (P = 0.044) and poor or intermediate prognosis chromosomal aberrations (P < 0.001). Conclusion: A TK level of >8.5 U/L best identified patients with progressive disease. Elevated TK levels could identify patients categorised, at diagnosis, into good prognosis subgroups by the various biological markers (mutated IgVH, good prognosis chromosomal aberrations, Zap-70− and CD38−) who subsequently showed disease progression. Additionally, patients with VH3-21 gene usage showed high TK levels, irrespective of mutational status, and serum TK measurement retained predictive power as disease progressed in all subcategories studied.

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