Analysis of ZAP70 expression in adult acute lymphoblastic leukaemia by real time quantitative PCR

Geothy Chakupurakal,Paul Moss,Mike Griffiths,Farooq Wandroo,Andrew Bell

doi:10.1186/1755-8166-5-22

Geothy Chakupurakal, Paul Moss + Show 3 more

Open Access

https://doi.org/10.1186/1755-8166-5-22

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Abstract

BackgroundZAP70 gene expression is associated with poor prognosis in B-cell lymphoproliferative disorders especially chronic lymphocytic leukaemia (CLL) but its role in adult B-ALL has not been established. On diagnostic samples from 76 patients with adult ALL (65 with B-ALL and 11 with T-ALL) ZAP70 mRNA expression levels were studied by real time-quantitative PCR (RT-qPCR) analysis.FindingsA broad distribution of ZAP70 expression was observed in ALL, ranging from 0.002 to 5.3 fold that of the ZAP70 positive Jurkat reference cell line. No association was observed between expression levels and the presence of specific cytogenetic abnormalities. Five cases, including one case of T-ALL, had ZAP70 expression above the level of the Jurkat reference cell line.ConclusionsOur results confirm the frequent expression of ZAP70 in adult ALL. Limited comparisons made did highlight poor-risk patients with high ZAP70 expression, but due to lack of clinical information on patient samples we were unable to directly assess the impact on disease prognosis. ZAP-70 may be an important laboratory assay in adult ALL and further studies are warranted to study a potential correlation with cytogenetic and other genetic markers.

Highlights

ZAP70 gene expression is associated with poor prognosis in B-cell lymphoproliferative disorders especially chronic lymphocytic leukaemia (CLL) but its role in adult B-ALL has not been established
ZAP70 mRNA expression was measured as fold increase/decrease relative to expression levels in the reference ZAP70 positive Jurkat cell line Table 1
ZAP70 expression was seen in all cases of T-ALL (Figure 1b)

Summary

Introduction

ZAP70 gene expression is associated with poor prognosis in B-cell lymphoproliferative disorders especially chronic lymphocytic leukaemia (CLL) but its role in adult B-ALL has not been established. Zeta associated protein tyrosine kinase (ZAP70) is a 70kD molecule associated with the ζ-chain of the CD3 T-cell receptor (TCR) complex [1]. The ζ-chains become docking sites for ZAP70 thereby activating the MAP kinase, calcium/calcineurin and protein kinase C signalling pathways. ZAP70 plays a major part in lymphocyte signal transduction resulting in cell differentiation and proliferation [2]. ZAP70 gene expression plays a critical role in the transition of pre-B to pro-B cells within the bone marrow. Genetic inactivation of the ZAP70 gene results in failure of pre-B cell receptor (pre-BCR) induced differentiation, proliferation and heavy chain exclusion, and a failure to

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