ZAP-70 in Mice and Men

[Guest guest]

Leuk Lymphoma. 2005 Dec;46(12):1689-98.

ZAP-70 in B cell malignancies.

Orchard J, Ibbotson R, Best G, A, Oscier D.

Departments of Haematology and Molecular Biology, Royal Bournemouth

Hospital, Bournemouth, UK.

ZAP-70 has emerged as a protein of potential prognostic importance in

chronic lymphocytic leukemia (CLL) following gene expression

profiling which compared the 2 well established prognostic sub-sets,

those with unmutated and mutated IgVH genes. This protein tyrosine

kinase (PTK), known to be of importance in T and NK cell signaling

but absent in normal peripheral B cells, is expressed in the majority

of the poorer prognosis unmutated CLL and absent in most cases with

mutated IgVH genes.

ZAP-70 has been shown to be functionally important in the CLL cases

in which it is expressed; it is also important in B cell development

in mice and there is preliminary evidence for its expression in human

B cell progenitors and activated B cells. Whether its expression in a

sub-set of CLL cases is a result of a more activated cell type or a

reflection of the stage of maturation of the transforming event(s) in

CLL is open to debate.

ZAP-70 is expressed in a minority of other B cell tumors but

correlation with IgVH gene mutational status is lacking.

The problems with ZAP-70 measurement, which has yet to be

standardized, are reviewed together with its current status as a

prognostic marker in CLL.

PMID: 16263570 [PubMed - in process]