7535

ZAP70

SRK|STD|TZK|ZAP-70;zeta-chain (TCR) associated protein kinase 70kDa;ZAP70;zeta-chain (TCR) associated protein kinase 70kDa

70 kDa zeta-associated protein|70 kDa zeta-chain associated protein|syk-related tyrosine kinase|tyrosine-protein kinase ZAP-70|zeta-chain associated protein kinase, 70kD

2q12

protein-coding

BACKGROUND: Zeta-chain-associated protein (ZAP- 70) is a 70kD adaptor protein that acts quickly after T cell activation to propagate signal. The role of ZAP-70 in Tcell function is well established, and in the previous years, this molecule was considered to be T-cell specific. More recent data have documented a role ofZAP-70 in B cells. Interest in ZAP-70 has grown since it has been shown, throughgene expression profiling, that it is expressed in a subset of cases of chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL). PURPOSE: The aim of this study was to investigate the expression of ZAP-70 in leukemic blasts of 50 newly diagnosed patients of B-lineage acute lymphoblastic leukemia (ALL), and toassess the correlation between ZAP-70 expression and various prognostic factors and outcome. PATIENTS AND METHODS: This study included 50 pediatric patients with newly diagnosed B-lineage ALL. They were 28 males (56% ) and 22 females (44% ) presented to the pediatric Oncology Department, National cancer Institute, CairoUniversity, during the period from 2005 to 2007. The age range was 2 to 17 yearswith a mean of 8.58+/-5.8 years and median 8 years. ALL patients were subjected at presentation to a full clinical history and physical examination. Patients diagnosed with ALL were enrolled on St. Jude Total XV protocol: standard risk and low risk according to results of primary investigation. Immunophenotyping was done using monoclonal antibodies which were analyzed on Coulter XL (Panel included CD1, CD2, CD3, CD4, CD5, CD7, CD8, CD10, CD19, CD22, Cytoplasmic m, anti k, anti l, CD13, CD33, anti classII MHC and TdT). Cases were considered ZAP-70 positive when exhibiting a ZAP/GAPDH (Glyceraldehyde- 3-phosphate dehydrogenase)ratio >or= 0.13. RESULTS: The study revealed expression of ZAP-70 in 5/50 cases (10% ). There was no statistically significant relation between ZAP-70 expression and the following: age, Total Leukocytic Count, hepatomegaly and splenomegaly. There was a correlation however between ZAP-70- expression and sex. Four patients died of disease progression: one patient with positive ZAP-70 expression and 3 patients with negative ZAP-70 expression. Fifteen patients (30% ) relapsed afterachieving complete remission (CR) and 3 patients (6% ) did not achieve CR. Four patients of those who relapsed had positive ZAP-70 expression. The 2.5 years DFSwas 73.1% for negative ZAP-70 cases while it was 20% in positive ZAP-70 cases. There was a statistically significant difference between 2.5-year DFS and ZAP-70expression (p=0.048). The Overall Survival at 2.5-years for negative ZAP-70 cases was 93.3% while it was 80% for positive ZAP-70 cases with p-value =0.27. CONCLUSIONS: Our results show that in B-Lineage ALL, ZAP-70 expression correlates with a worse DFS and an increased relapse rate. Furthermore, these results raisethe need of prospective trials to evaluate the possibility of designing new compounds targeting this protein.