ZAP-70, IgVh, and cytogenetics for assessing prognosis in chronic lymphocytic leukemia

Cancer Biomark. 2010;6(1):1-9. doi: 10.3233/CBM-2009-0114.

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.

Design and 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Area Under Curve
  • Biomarkers, Tumor / analysis*
  • Cell Separation
  • Cytogenetics / methods
  • Female
  • Flow Cytometry
  • Gene Deletion
  • Humans
  • Immunoglobulin Heavy Chains / genetics*
  • Immunoglobulin Variable Region / genetics*
  • In Situ Hybridization, Fluorescence
  • Leukemia, Lymphocytic, Chronic, B-Cell / genetics*
  • Leukemia, Lymphocytic, Chronic, B-Cell / pathology
  • Male
  • Middle Aged
  • Mutation
  • Prognosis
  • ROC Curve
  • Sensitivity and Specificity
  • ZAP-70 Protein-Tyrosine Kinase / biosynthesis*

Substances

  • Biomarkers, Tumor
  • Immunoglobulin Heavy Chains
  • Immunoglobulin Variable Region
  • ZAP-70 Protein-Tyrosine Kinase
  • ZAP70 protein, human