ZAP-70 in B cell malignancies.
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.
Orchard
Jenny
J
Department of Haematology, Royal Bournemouth Hospital, UK.
Ibbotson
Rachel
R
Best
Giles
G
Parker
Anton
A
Oscier
David
D
D001402:B-Lymphocytes / Q000201:enzymology; D014408:Biomarkers, Tumor / Q000032:analysis; D006801:Humans; D007694:Killer Cells, Natural / Q000201:enzymology; D015448:Leukemia, B-Cell / Q000201:enzymology*; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000201:enzymology*; D016393:Lymphoma, B-Cell / Q000201:enzymology; D011379:Prognosis; D015398:Signal Transduction; D013601:T-Lymphocytes / Q000201:enzymology; D051746:ZAP-70 Protein-Tyrosine Kinase / Q000378:metabolism*
D014408:Biomarkers, Tumor; D051746:ZAP-70 Protein-Tyrosine Kinase