ZAP-70 Quantitied by PCR in CLL

[Guest guest]

Author Stamatopoulos, Basile , Brussels, Bordet Institute Belgium

Co-author(s) Meuleman, Nathalie , Brussels, Bordet Institute

Haibe-Kains, , Brussels, Bordet Institute

Duvillier, Hugues , Brussels, Bordet Institute

Massy, e , Brussels, Bordet Institute

Martiat, Philippe , Brussels, Bordet Institute

Bron, Dominique , Brussels, Bordet Institute

Lagneaux, ce , Brussels, Bordet Institute

Background: Chronic Lymphocytic Leukemia (CLL) is a heterogeneous

disease with respect to prognosis and clinical outcomes. Two

different groups in terms of overall survival and clinical

characteristics are now classified on the IgVH mutational status.

However, this costly analysis is very laborious and surrogate

markers have been investigated.

Methods : We developed a standardised and quantitative PCR (qPCR)

method to measure Zap-70 mRNA (æ-associated protein 70) expression

in sorted CD19+ cells. The comparison of this method with others

(Zap-70 and CD38 by flow cytometry, and lipoprotein lipase (LPL)

mRNA by qPCR) was performed in a cohort of 108 patients with a

median follow up of 82 months to evaluate their association with

IgVH mutational status, overall survival (OS) and treatment-free

survival (TFS).

Results : The association between Zap-70 by qPCR and IgVH mutational

status was clearly significant [÷²=50.95; P< 0.0001] and

characterised by a Cramer's V statistic of 0.72 indicating a very

strong relation. This method also presents 87.8% sensitivity, 85.7%

sensibility, 87.5% positive predictive value and 86% negative

predictive value. Zap-70 expression was significantly associated

with OS [P=0.0021] and TFS [P< 0.0001]. Zap-70-positive patients had

a significantly shorter median TFS (24 months) than Zap-70-negative

patients (157 months). Moreover, Zap-70 by qPCR seems to have a

better prognostic power than IgVH mutational status and the other

prognostic marker tested.

Conclusions : Zap-70 mRNA expression quantified by real time PCR is

a strong surrogate marker of IgVH mutational status and a powerful

prognostic factor.