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.

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.

• Authors: Alessandra Trojani, Marco Montillo, Michele Nichelatti, Alessandra Tedeschi, Chiara Colombo, Silvio Veronese, Maria Angela Mura, Francesca Ricci, Barbara Scarpati, Anna Colosimo, Milena Lodola, Enrica Morra
• Journal: Cancer biomarkers : section A of Disease markers (Cancer Biomark) Vol. 6 Issue 1 Pg. 1-9 ( 2010) ISSN: 1875-8592 [Electronic] Netherlands
• PMID: 20164537 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

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

Topics

• 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, pathology)
• Male
• Middle Aged
• Mutation
• Prognosis
• ROC Curve
• Sensitivity and Specificity
• ZAP-70 Protein-Tyrosine Kinase (biosynthesis)