BACKGROUND: Chronic lymphocytic leukemia (CLL) is heterogeneous with respect to prognosis and clinical outcome. Mutational status of immunoglobulin heavy chain variable region (IGHV) appears to be a particularly strong prognostic marker, but it is difficult to perform in a routine clinical laboratory. ζ-chain-associated protein kinase 70 kDa (ZAP-70) protein detected by flow cytometry is a strong surrogate marker of IGHV mutational status; however, it suffers from the lack of standardization. METHODS: We investigated whether ZAP-70 mRNA expression level can be a prognostic factor in CLL. Real-time quantitative polymerase chain reaction was used to analyze ZAP-70 mRNA expression from 102 CLL patients. RESULTS: The expression of ZAP-70 mRNA was significantly associated with Binet stage (P < 0.001), lactate dehydrogenase (P = 0.003), ZAP-70 protein (P = 0.018), IGHV mutational status (P = 0.038), and cytogenetic abnormality of del(17p13) or del(11q22.3) (P = 0.037) in CLL patients. According to receiver operating characteristic curve analysis for ZAP-70 mRNA and ZAP-70 protein, positive ZAP-70 mRNA (P = 0.006) was an adverse factor in determining the treatment free survival (TFS). In a multivariate Cox analysis of TFS, ZAP-70 mRNA is not ideal as an independent prognostic factor. However, ZAP-70 mRNA was statistically significant in predicting treatment response. CONCLUSION: This study demonstrated the value of determination of ZAP-70 mRNA in providing useful prognostic information in CLL patients. However, ZAP-70 mRNA is not an independent prognostic factor.
BACKGROUND:Chronic lymphocytic leukemia (CLL) is heterogeneous with respect to prognosis and clinical outcome. Mutational status of immunoglobulin heavy chain variable region (IGHV) appears to be a particularly strong prognostic marker, but it is difficult to perform in a routine clinical laboratory. ζ-chain-associated protein kinase 70 kDa (ZAP-70) protein detected by flow cytometry is a strong surrogate marker of IGHV mutational status; however, it suffers from the lack of standardization. METHODS: We investigated whether ZAP-70 mRNA expression level can be a prognostic factor in CLL. Real-time quantitative polymerase chain reaction was used to analyze ZAP-70 mRNA expression from 102 CLLpatients. RESULTS: The expression of ZAP-70 mRNA was significantly associated with Binet stage (P < 0.001), lactate dehydrogenase (P = 0.003), ZAP-70 protein (P = 0.018), IGHV mutational status (P = 0.038), and cytogenetic abnormality of del(17p13) or del(11q22.3) (P = 0.037) in CLLpatients. According to receiver operating characteristic curve analysis for ZAP-70 mRNA and ZAP-70 protein, positive ZAP-70 mRNA (P = 0.006) was an adverse factor in determining the treatment free survival (TFS). In a multivariate Cox analysis of TFS, ZAP-70 mRNA is not ideal as an independent prognostic factor. However, ZAP-70 mRNA was statistically significant in predicting treatment response. CONCLUSION: This study demonstrated the value of determination of ZAP-70 mRNA in providing useful prognostic information in CLLpatients. However, ZAP-70 mRNA is not an independent prognostic factor.
Authors: T Vincent Shankey; Meryl Forman; Paul Scibelli; Jeffrey Cobb; Cecilia M Smith; Rhonda Mills; Karen Holdaway; Elizabeth Bernal-Hoyos; Mafalda Van Der Heiden; Jan Popma; Mike Keeney Journal: Cytometry B Clin Cytom Date: 2006-07-15 Impact factor: 3.058
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Authors: J L Binet; A Auquier; G Dighiero; C Chastang; H Piguet; J Goasguen; G Vaugier; G Potron; P Colona; F Oberling; M Thomas; G Tchernia; C Jacquillat; P Boivin; C Lesty; M T Duault; M Monconduit; S Belabbes; F Gremy Journal: Cancer Date: 1981-07-01 Impact factor: 6.860
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