title: ZAP-70, IgVh, and cytogenetics for assessing prognosis in chronic lymphocytic leukemia.
abstract: BACKGROUND
  New prognostic factors such as IgVh mutational status, ZAP-70 protein expression and cytogenetic abnormalities have shown to offer important prognostic information for patients with chronic lymphocytic leukemia (CLL). Our aim was to evaluate the optimal cut-off for IgVh mutational status, ZAP-70 expression and cytogenetic abnormalities in association with disease progression defined as the need for treatment within 3~years from diagnosis in 170 patients with B-CLL.
  
  
  METHODS
  Receiver operating characteristics (ROC) analysis and multivariate general linear models (GLMs) were used to investigate the most significant cut-off values of these biomarkers and their prognostic impact.
  
  
  RESULTS
  Our findings estimated that the optimal cut-off for IgVh mutation status and for ZAP-70 protein expression was 97% and 16.5% respectively and a high concordance between the two was demonstrated. We identified 30% as being the best-cut-off for 17p-, 11q- and 6q-. In univariate analysis 17p- was found to be a significant predictor of the event only for the whole population. Multivariate analysis including all biological parameters, identified 11q deletion as the only significant regressor.
  
  
  CONCLUSIONS
  We assessed that IgVh mutational status, ZAP-70 protein and 6q- are powerful prognostic markers. Analyses of all these factors revealed that 11q deletion was the strongest predictor of disease progression in B-CLL.
authors.affiliation: Niguarda Cà Granda Hospital, Division of Hematology, Milan, Italy. alessandra.trojani@ospedaleniguarda.it
authors.forename: Alessandra
authors.initials: A
authors.lastname: Trojani
authors.forename: Marco
authors.initials: M
authors.lastname: Montillo
authors.forename: Michele
authors.initials: M
authors.lastname: Nichelatti
authors.forename: Alessandra
authors.initials: A
authors.lastname: Tedeschi
authors.forename: Chiara
authors.initials: C
authors.lastname: Colombo
authors.forename: Silvio
authors.initials: S
authors.lastname: Veronese
authors.forename: Maria Angela
authors.initials: MA
authors.lastname: Mura
authors.forename: Francesca
authors.initials: F
authors.lastname: Ricci
authors.forename: Barbara
authors.initials: B
authors.lastname: Scarpati
authors.forename: Anna
authors.initials: A
authors.lastname: Colosimo
authors.forename: Milena
authors.initials: M
authors.lastname: Lodola
authors.forename: Enrica
authors.initials: E
authors.lastname: Morra
mesh_terms: D000328:Adult; D000368:Aged; D019540:Area Under Curve; D014408:Biomarkers, Tumor / Q000032:analysis*; D002469:Cell Separation; D003582:Cytogenetics / Q000379:methods; D005260:Female; D005434:Flow Cytometry; D017353:Gene Deletion; D006801:Humans; D007143:Immunoglobulin Heavy Chains / Q000235:genetics*; D007135:Immunoglobulin Variable Region / Q000235:genetics*; D017404:In Situ Hybridization, Fluorescence; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000235:genetics* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009154:Mutation; D011379:Prognosis; D012372:ROC Curve; D012680:Sensitivity and Specificity; D051746:ZAP-70 Protein-Tyrosine Kinase / Q000096:biosynthesis*
chemical_list: D014408:Biomarkers, Tumor; D007143:Immunoglobulin Heavy Chains; D007135:Immunoglobulin Variable Region; D051746:ZAP-70 Protein-Tyrosine Kinase; C497261:ZAP70 protein, human