Additional Genetic High-Risk Features Such As 11q Deletion, 17p Deletion, and V3-21 Usage Characterize Discordance of ZAP-70 and VH Mutation Status in Chronic Lymphocytic Leukemia

• DOI: 10.1200/jco.2005.03.7184
• Publication Date: 2006-01-18T03:43:34Z
• Authors: Alexander Kröber; Johannes Bloehdorn; Sebastian Hafner; Andreas Bühler; Till Seiler; Dirk Kienle; Dirk Winkler; Markus Bangerter; Richard F. Schlenk; Axel Benner; Peter Lichter; Hartmut Döhner; Stephan Stilgenbauer
• Keywords: Concordance

Immunoglobulin heavy chain variable-region (VH) gene mutation status and zeta-associated protein 70 (ZAP-70) expression are correlated in chronic lymphocytic leukemia (CLL), but their concordance is variable. The goal of this study was to elucidate additional factors potentially characterizing discordance.We evaluated ZAP-70 by flow cytometry, VH DNA sequencing, genomic aberrations fluorescence situ hybridization 148 CLL patients. parameters were analyzed for associations individual prognostic impact.ZAP-70 strongly associated without genetic high-risk-features as defined the absence 11q or 17p deletion V3-21 usage (concordance 84%). In contrast, proportion discordant cases significantly higher (39%), if such high-risk features present. Discordant with almost exclusively positive mutated (89%), whereas all one negative unmutated (92%). By multivariate regression analysis, two models developed, which both include and, alternatively, independent outcome predictors.There characteristic modes discordance between depending on presence usage. Although biologic background these findings yet be determined, data have clinical implications regarding a pathogenic factor predictor, respectively.