- Lancet. 2004 Jan
10;363(9403):105-11.
ZAP-70 expression and prognosis in chronic
lymphocytic leukaemia.
Orchard JA, Ibbotson RE, Davis Z, Wiestner A, Rosenwald A,
Thomas PW, Hamblin TJ, Staudt LM, Oscier DG.
Department of Haematology, Royal Bournemouth Hospital,
Bournemouth, UK.
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-70 positive (hazard ratio 5.5,
2.8-.8). INTERPRETATION: ZAP-70 protein, which can be measured
by flow cytometry in the general laboratory, is a reliable
prognostic marker in CLL, equivalent to that of IgVH gene
mutational status.
PMID: 14726163 [PubMed - indexed for MEDLINE]
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