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Blood, 1 August 2006, Vol. 108, No. 3, pp. 853-861. Prepublished online as a Blood First Edition Paper on April 6, 2006; DOI 10.1182/blood-2005-12-4986. This Article Full Text Full Text (PDF) All Versions of this Article: 2005-12-4986v1 108/3/853    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Del Principe, M. I. Articles by Amadori, S. Search for Related Content PubMed PubMed Citation Articles by Del Principe, M. I. Articles by Amadori, S. Related Collections Neoplasia Signal Transduction Free Research Articles Clinical Trials and Observations Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  CLINICAL TRIALS AND OBSERVATIONS Clinical significance of ZAP-70 protein expression in B-cell chronic lymphocytic leukemia Maria Ilaria Del Principe, Giovanni Del Poeta, Francesco Buccisano, Luca Maurillo, Adriano Venditti, Antonella Zucchetto, Rita Marini, Pasquale Niscola, Maria Antonietta Irno Consalvo, Carla Mazzone, Licia Ottaviani, Paola Panetta, Antonio Bruno, Riccardo Bomben, Giovanna Suppo, Massimo Degan, Valter Gattei, Paolo de Fabritiis, Maria Cantonetti, Francesco Lo Coco, Domenico Del Principe, and Sergio Amadori From the Cattedra di Ematologia, Università Tor Vergata, Roma, Italy; the Clinical and Experimental Hematology Research Unit, Centro di Riferimento Oncologico, Aviano (PN), Italy, and the Clinica Pediatrica, Università Tor Vergata, Roma, Italy. The clinical course of B-cell chronic lymphocytic leukemia (B-CLL) is variable, and novel biologic parameters need to be added to the clinical staging systems to predict an indolent or aggressive outcome. We investigated the 70-kDa zeta-associated protein (ZAP-70), CD38, soluble CD23 (sCD23), and cytogenetics in 289 patients with B-CLL. Both a shorter progression-free survival (PFS) and overall survival (OS) were observed in ZAP-70+ (P < .001), in CD38+ (P < .001) and in sCD23+ patients (P < .001 and P = .013, respectively). ZAP-70+CD38+ or ZAP-70+ patients with an unmutated IgVH status showed both a shorter PFS (P < .001) and OS (P < .001 and P < .001, respectively) as compared with ZAP-70–/CD38– or ZAP-70– patients with mutated IgVH genes. Discordant patients showed an intermediate outcome. Note, ZAP-70+ patients even if CD38– or mutated showed a shorter PFS, whereas ZAP-70– patients even if CD38+ or unmutated had a longer PFS. Furthermore, ZAP-70 positivity was associated with a shorter PFS both within normal karyotype (P < .001) and within the poor-risk cytogenetic subset (P = .02). The predictive value of ZAP-70 expression was confirmed in multivariate analysis. Thus, ZAP-70 protein determined by flow cytometry improves the prognostic significance of cytogenetics and appears to be a better predictor of outcomes than IgVH gene mutational status. On this line, we recommend and are also interested in conducting a prospective randomized trial of early intervention versus observation for ZAP-70+ patients. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: L. Kujawski, P. Ouillette, H. Erba, C. Saddler, A. Jakubowiak, M. Kaminski, K. Shedden, and S. N. Malek Genomic complexity identifies patients with aggressive chronic lymphocytic leukemia Blood, September 1, 2008; 112(5): 1993 - 2003. [Abstract] [Full Text] [PDF] L. Z. 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