ZAP-70 (ZAP70) Antibody Review





  • 70-kd Zeta-associated protein. PMID: 16938520

  • an important negative prognostic factor in chronic lymphocytic leukemia (CLL). PMID: 17038529

  • one of the most studied prognostic markers in Chronic Lymphocytic Leukemia (CLL). PMID: 16906579

  • plays a pivotal role in interferon-stimulated MAPK activation. PMID: 16219325

  • a surrogate marker for immunoglobulin heavy-chain variable region (IgV(H)) mutation status, which is known as a prognostic marker in B-cell chronic lymphocytic leukemia (CLL). PMID: 16906585, PMID: 16906582

  • a member of the Syk/ZAP protein tyrosine kinase family, normally expressed in T cells and NK cells but not found in normal, mature B cells. PMID: 15871558, PMID: 9535797

Normal Expression

  • Among normal B-cell subsets, ZAP-70 was found expressed in normal pro/pre B cells but not in a significant proportion of normal B cells with mature phenotype. PMID: 16467082

  • ZAP-70 gene is normally expressed in T and natural killer cells, where it is required for the T-cell receptor (TCR) signaling. PMID: 16467082

  • ZAP-70 is expressed in a subpopulation of tonsillar and splenic normal B-lymphocytes that express an activated phenotype. Furthermore, ZAP-70 expression can be induced in vitro upon stimulation of blood and tonsillar B cells. PMID: 15800671

  • ZAP-70 is a tyrosine kinase expressed in normal T cells and NK cells. PMID: 15487457

  • By immunoblot and immunoprecipitation assay using various anti-ZAP-70 antibodies, a 66 kDa tyrosine kinase was detected in lysates from rat brain. During the development of rat brain, expression levels of this 66 kDa tyrosine kinase were highest around 3 weeks after birth and decreased thereafter in the adult. In addition, immunoblot analysis demonstrated that this 66 kDa tyrosine kinase was expressed almost solely in the nervous system. PMID: 9535797

  • Initial experiments in epithelial cells indicated that ZAP-70 is diffusely located throughout the quiescent cell, and accumulates at the plasma membrane upon cellular activation. Intriguingly, a large amount of ZAP-70, both chimeric and endogenous, resides in the nucleus of quiescent and activated cells. Nuclear ZAP-70 becomes tyrosine phosphorylated upon stimulation via the T cell receptor, indicating that it may have an important biologic function. PMID: 9362531

Abnormal Expression

  • ZAP-70 is expressed by many lymphoma types, correlates with immunoglobulin heavy-chain variable region gene mutational status in chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL), and can be detected reliably using immunohistochemical methods. PMID: 15133473


  • high levels of ZAP-70 correlated with Binet stages B or C indicating an involvement of ZAP-70 in mechanisms promoting growth of B-CLL cells. PMID: 15370248

  • ZAP-70 plays an important role in growth, differentiation, and function of not only T cells but also nerve cells and several embryonic tissues. PMID: 7553892

Diagnostic and Therapeutic Value

  • immunohistological detection of ZAP-70 on formalin-fixed BM biopsies at diagnosis appears a useful methodological approach to identify patients with poor prognosis in chronic lymphocytic leukaemia (CLL). PMID: 17082778

  • ZAP-70 reactivity using a T-cell marker as a control allows to identify the majority of patients with an unmutated Ig VH genotype. PMID: 17051526

  • although ZAP-70 positivity correlates with IgV(H) mutation status and survival, variations in sample handling and preparation may influence results. ZAP-70 testing should not be used as the sole criterion for stratifying patients for therapy. PMID: 16906585

  • Patients with a low percentage (<20%) of ZAP-70 positive neoplastic B lymphocytes have a much better prognosis that those with a higher proportion (>20%) of ZAP-70 positive neoplastic B lymphocytes. PMID: 16906580

  • ZAP-70 expression could become a key parameter to guide patients towards risk adapted treatment strategies in prospective clinical trials. PMID: 16906579

  • ZAP-70 protein determined by flow cytometry improves the prognostic significance of cytogenetics and appears to be a better predictor of outcomes than IgV(H) gene mutational status. PMID: 16601244

  • ZAP-70 expression is not a CLL-specific feature among B-cell malignancies and suggest that the absence of ZAP-70 rather than its presence should be considered abnormal for malignant B lymphocytes. PMID: 16482211

  • ZAP-70 immunoreactivity can be a reliable prognostic marker in chronic lymphocytic leukemia (CLL) and proposes a system for evaluating the results. The observations support the inclusion of the immunohistochemical expression of ZAP-70 in clinical trials involving CLL patients. PMID: 16321853

  • ZAP-70 protein, which can be measured by flow cytometry in the general laboratory, is a reliable prognostic marker in chronic lymphocytic leukaemia (CLL), equivalent to that of IgVH gene mutational status. PMID: 14726163

Review Articles



Flow Cytomery (FC)

  • Fifty-three consecutive B-CLL cases were included in the study. ZAP-70 expression was investigated by flow cytometry. PMID: 17051526

  • National standardization of ZAP-70 determination by flow cytometry: The French experience. PMID: 17041946

  • Evaluation of ZAP-70 expression by flow cytometry in chronic lymphocytic leukemia: A multicentric international harmonization process. PMID: 16906588

  • Flow cytometric analyses for ZAP-70 were performed in peripheral blood samples from 145 B-CLL (124 with IgV(H) mutations) by a standard three-color protocol. PMID: 16906587

  • We developed a system using the 8-peak Rainbow beads as our fluorescence calibrator along with a fixed cell control. Using a panel of CD19-PE, CD5-FITC, and ZAP-70-Alexa 647, we stained normal whole blood, and blood and bone marrow from patients with CLL to determine the level of ZAP-70 expression in T-cell, B-cell, and CLL-cell populations. PMID: 16906586

  • Use of a blocking antibody method for the flow cytometric measurement of ZAP-70 in B-CLL. PMID: 16906584

  • flow cytometric analysis of ZAP-70 suffers from difficulties in standardization and interpretation. We applied the Kolmogorov-Smirnov (KS) statistical test to make analysis more straightforward. PMID: 16906582

  • An optimized whole blood method for flow cytometric measurement of ZAP-70 protein expression in chronic lymphocytic leukemia. PMID: 16906581

  • Comparison of bone marrow and peripheral blood ZAP-70 status examined by flow cytometric immunophenotyping in patients with chronic lymphocytic leukemia. PMID: 16906578

  • We compared different staining methods utilizing monoclonal antibodies (moAb) against ZAP-70: anti-ZAP-70 PE, clone 1E7.2, anti-ZAP-70 PE, clone 17A/P-ZAP70 directly stained with flourochrome as well as anti-ZAP-70 antibody, clone 2F3.2 stained with Zenontrade mark Alexa Fluor(R) 488 Labeling Kit. PMID: 16906577

  • different gating strategies for determining flow cytometric ZAP-70 expression status produce highly discordant results. Further standardization is required before ZAP-70 can be used as a reliable prognostic parameter in immunophenotyping of B-CLL. PMID: 16906574

  • ZAP-70 by flow cytometry: a comparison of different antibodies, anticoagulants, and methods of analysis. PMID: 16906573

  • Feasibility of an easily applicable method of ZAP-70 measurement in chronic lymphocytic leukemia in the routine flow cytometry setting: a methodological approach. PMID: 16871389

  • Quantitative flow cytometry of ZAP-70 levels in chronic lymphocytic leukemia using molecules of equivalent soluble fluorochrome. PMID: 16456869

  • A robust ratio metric method for analysis of Zap-70 expression in chronic lymphocytic leukemia (CLL). PMID: 16342060

  • Comparison of flow cytometric methods for the measurement of ZAP-70 expression in a routine diagnostic laboratory. PMID: 16048494

Immunocytochemistry (ICC)

  • We modified the method of immunocytochemical assessment of ZAP-70 expression. The traditional two-step method with monoclonal anti-ZAP-70 antibody in the first step followed by FITC-conjugated goat anti-mouse IgG was changed for one-step method with monoclonal anti-ZAP-70 antibody labeled by Zenon Alexa Fluor 488. PMID: 15871558

Immunohistochemistry (IHC)

  • ZAP-70 expression, as detected by immunohistochemistry on bone marrow biopsies from early-phase chronic lymphocytic leukemia (CLL) patients, is a strong adverse prognostic factor. PMID: 17082778

  • The expression of ZAP-70, detected by an immunohistochemical assay and also by real-time quantitative reverse transcriptase-polymerase chain reaction assigned 83% of the chronic lymphocytic leukemia cases to the suspected immunoglobulin mutation subtype. PMID: 16938520

  • The aim was to determine the prognostic significance of the immunohistochemical expression of ZAP-70 protein in chronic lymphocytic leukemia (CLL) by means of the long-term follow-up of 108 patients. PMID: 16321853

  • Immunohistochemical analysis represents an effective method for assessing ZAP-70 expression and reveals that a variety of B-cell malignant neoplasms express ZAP-70, albeit at low frequency. PMID: 16280661

  • In this study ZAP-70 expression was studied by immunohistochemistry in a spectrum of B-cell lymphoid neoplasms; this staining method was compared with flow cytometry, and the relationship of ZAP-70 expression to mutational status and prognosis was assessed. PMID: 15685592

  • We examined 446 specimens representing a range of hematopoietic malignant neoplasms for ZAP-70 expression by immunohistochemical analysis. PMID: 15487457

  • Using immunohistochemical methods, we evaluated zeta-associated protein (ZAP)-70 expression in 341 cases of non-Hodgkin and Hodgkin lymphoma. PMID: 15133473

Immunoprecipitation (IP)

  • By immunoblot and immunoprecipitation assay using various anti-ZAP-70 antibodies, a 66 kDa tyrosine kinase was detected in lysates from rat brain. PMID: 9535797

Western Blotting (WB)

  • ZAP-70 expression was ascertained by flow cytometry, immunofluorescence, Western blot, and quantitative reverse transcription-PCR. PMID: 16467082

  • The expression of ZAP-70 was analyzed in T-cell and B-cell lines and in peripheral-blood samples from 56 patients with CLL with the use of flow cytometry, Western blotting, and immunohistochemistry. PMID: 12724482