ZAP-70 in B cell malignancies: Leuk Lymphoma

Jenny Orchard, Rachel Ibbotson, Giles Best, Anton Parker, David Oscier

Research output: Contribution to journalArticlepeer-review

27 Citations (Scopus)

Abstract

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.
Original languageEnglish
Pages (from-to)1689-1698
Number of pages10
JournalLeukemia and Lymphoma
Volume46
Issue number12
DOIs
Publication statusPublished - Dec 2005
Externally publishedYes

Keywords

  • B-Lymphocytes/enzymology Biomarkers, Tumor/analysis Humans Killer Cells, Natural/enzymology Leukemia, B-Cell/*enzymology Leukemia, Lymphocytic, Chronic, B-Cell/*enzymology Lymphoma, B-Cell/enzymology Prognosis Signal Transduction T-Lymphocytes/enzymology ZAP-70 Protein-Tyrosine Kinase/*metabolism

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