ZAP-70 Tyrosine Kinase Is Constituvely Expressed and Phosphorylated in B-Lineage Acute Lymphoblastic Leukemia Cells.

Zeta-associated protein 70 (ZAP-70), a member of the Syk family of protein tyrosine kinases is normally expressed in T and NK cells. ZAP-70 plays a key role in the signaling pathway of the TCR. It has been recently shown that this protein is also expressed in mouse B lineage cells. While little is known about ZAP-70 expression in normal human B cells, it has been reported that ZAP-70 is expressed in a subset of chronic lymphocytic leukemia (CLL), with a poor prognosis, that have nonmutated immunoglobulin variable region genes.

In this study, we examined the expression and phosphorylation status of ZAP-70 and Syk in B-lineage acute lymphoblastic leukemia (B-ALL) cells. ZAP-70 and Syk were constitutively expressed and phosphorylated (tyr319 for ZAP and tyr352 for Syk) in human precursor B-ALL cell lines as well as in B leukemic cells from all examined B-ALL patients (n=18). The expression of ZAP-70 was specific to these B-ALL cells as it was not detected in the K562 cell line or malignant myeloid cells. This expression was independant of maturation state of leukemic cells (pro-B or pre-B) and caryotypic status.

The expression and phosphorylation of the T-cell “specific” ZAP-70 kinase in all B-ALL cells raises important questions concerning the contribution of this protein to the leukemogenesis process resulting in B-ALL.