title: Serum TK levels in CLL identify Binet stage A patients within biologically defined prognostic subgroups most likely to undergo disease progression.
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 IgV(H) 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. IgV(H) mutational status and V(H) 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 IgV(H) unmutated, compared with IgV(H) 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).
  
  
  CONCLUSIONS
  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 IgV(H), good prognosis chromosomal aberrations, Zap-70(-) and CD38(-)) who subsequently showed disease progression. Additionally, patients with V(H)3-21 gene usage showed high TK levels, irrespective of mutational status, and serum TK measurement retained predictive power as disease progressed in all subcategories studied.
authors.affiliation: Department of Haematology, Belfast City Hospital, Belfast, UK.
authors.forename: Christine
authors.initials: C
authors.lastname: Matthews
authors.forename: Mark A
authors.initials: MA
authors.lastname: Catherwood
authors.forename: T C M
authors.initials: TC
authors.lastname: Morris
authors.forename: Paul J
authors.initials: PJ
authors.lastname: Kettle
authors.forename: Mary B
authors.initials: MB
authors.lastname: Drake
authors.forename: William S
authors.initials: WS
authors.lastname: Gilmore
authors.forename: H Denis
authors.initials: HD
authors.lastname: Alexander
mesh_terms: D051997:ADP-ribosyl Cyclase 1 / Q000235:genetics; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002869:Chromosome Aberrations; D018450:Disease Progression; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D007135:Immunoglobulin Variable Region / Q000235:genetics; D017404:In Situ Hybridization, Fluorescence; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000097:blood* / Q000201:enzymology / Q000235:genetics / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009154:Mutation; D011379:Prognosis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013937:Thymidine Kinase / Q000097:blood*
chemical_list: D007135:Immunoglobulin Variable Region; D013937:Thymidine Kinase; D051997:ADP-ribosyl Cyclase 1