Zeta Chain-Associated Protein-70 Expression is a Prognostic Tool in Mature and Precursor B-Cell Neoplasm

Abstract

Problem statement: The Zeta Chain-Associated Protein (ZAP) is a 70-kDa molecule associated with the zeta chain of the CD3 receptor complex of the lymphocyte population. It plays an important role in signaling initiation, activation T-cell receptor, phosphorylation of multiple downstream targets. So that believed as T. lymphocyte specific .Several studies is gathering that the pattern of expression is not lineage specific. We aimed to study the role of ZAP-70 /CD38 as new prognostic marker in CLL and its prognostic value in ALL patients. Approach: Our study included 49 ALL ranged from 2-42 years they were 27 males and 22 females. One hundred fifty six patients with CLL. They were 87 males and 69 females, their ages ranged from 50-77 yearsImmunophenotyping. by flow cytometry (EPICS XL-2and 4 color Bechman Coulter USA), intracellular ZAP70 protein was assessed by flow cytometry using (Caltag laboratories, Beckman Coulter USA). Results: Immunophenotyping of 49 ALL patients ZAP-70 was found at significantly higher levels in T-ALL cases compared with B-lineage (p<0.001), however, a proportion of B- lineage ALL showed high levels of ZAP-70. Moreover we observed that ZAP-70 is higher in pre-B ALL than pro B ALL and common ALL with more decline in mature B-ALL. Follow up patient by zap, pretreatment versus post treatment p = 0.008, correlation of zap with hematological and clinical parameter in ALL, no significant correlation except positively correlated with leucocytic count while in CLL highly significant correlation with splenomegally but not with lymphadenopathy, strong association between zap-70 and binnet staging but not with CD38. Overall survival of zap-70 in ALL/CLL show that short free survival associated with positive zap-70. ZAP-70 has raised great interest in CLL patients because it represents a powerful prognostic marker. Conclusion: Our results provide preliminary indication on the potential use of this protein as a prognostic marker also in ALL. These results clearly show that ZAP-70 may indeed be a therapeutic target. ZAP-70 expression in a subset of patients with ALL opens the perspective of investigating the use of an inhibitor and can be a candidate molecule for targeted therapy.