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ZAP-70 expression and prognosis in chronic lymphocytic leukaemia.

Orchard, Jenny A, Ibbotson, Rachel E, Davis, Zadie, Wiestner, Adrian, Rosenwald, Andreas, Thomas, Peter W, Hamblin, Terry J, Staudt, Louis M, Oscier, David G·2004·The Lancet
DOI 10.1016/s0140-6736(03)15260-9
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Abstract

Background Chronic lymphocytic leukaemia (CLL) is a heterogeneous disease; many patients never need treatment, whereas some have poor outcomes. New treatments, which can induce complete remissions, allow patients with poor outlook to be treated while they are still asymptomatic. Whether or not the IgVH gene is mutated is the best predictor of clinical outcome, but this assay is unsuited to the routine laboratory. The gene coding for ZAP-70, a tyrosine kinase protein normally expressed in T and NK cells, has been shown by gene-expression profiling to be differentially expressed between patients with mutated and unmutated IgVH genes. We assessed whether ZAP-70 could be used as a prognostic marker in CLL. Methods We developed a flow cytometry assay for ZAP-70 protein expression and investigated its concordance with ZAP-70 mRNA expression, IgVH gene mutational status, and clinical outcome in 167 patients with CLL. Findings We showed high concordance between ZAP-70 protein expression and IgVH gene mutations. 108 patients (65%) had mutated IgVH genes and were ZAP-70 negative; 46 (28%) had unmutated IgVH genes and were ZAP-70 positive. Findings were discordant in 13 patients: six (4%) had mutated IgVH genes but were ZAP-70 positive, and seven (4%) had unmutated IgVH genes and were ZAP-70 negative. Expression of mRNA showed 97% concordance with ZAP-70 protein. Median survival was 24.4 years (95% CI 15.1-33.8) in ZAP-70 negative patients and 9.3 years (7.0-11.5) in those who were ZAP-…

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Research works printed but not linked: 29

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Cited by

Metadata

Authors
Orchard, J. A., Ibbotson, R. E., Davis, Z., Wiestner, A., Rosenwald, A., Thomas, P. W., Hamblin, T. J., Staudt, L. M., & Oscier, D. G.
Venue
The Lancet
Publisher
Elsevier BV
Published
2004-01
Volume
363
Issue
9403
Pages
105-111
ISSN
0140-6736
DOI
10.1016/s0140-6736(03)15260-9
Cited by
448
References
0
Language
en
Licence
www.elsevier.com/tdm/userlicense/1.0/ (tdm)

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