ZAP-70 Expression in B-Cell Hematologic Malignancy Is Not Limited to CLL/SLL

Sup, Stephen J.; Domiati‐Saad, Rana; Kelley, Todd W.; Steinle, Roxanne; Zhao, Xinyu; Hsi, Eric D.

doi:10.1309/wvqp-vdf8-uf7a-v21x

Cited by 24 publications

(26 citation statements)

References 16 publications

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“…26 However, other groups, also in abstract form, report results similar to our own. 27,28 The reasons for the discrepancy between the preliminary results of Bano et al 26 compared with others are unknown. We would also not have anticipated ZAP-70 expression in one case of nodal marginal zone B-cell lymphoma and in one case of Burkitt lymphoma, as these neoplasms are believed to be of post germinal center cell origin, with somatic hypermutation IgV gene occurring in nearly all cases.…”

Section: Zap-70 In Hodgkin Lymphomasmentioning

confidence: 93%

Immunohistochemical detection of ZAP-70 in 341 cases of non-Hodgkin and Hodgkin lymphoma

et al. 2004

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Using immunohistochemical methods, we evaluated zeta-associated protein (ZAP)-70 expression in 341 cases of non-Hodgkin and Hodgkin lymphoma. In B-cell NHL, ZAP-70 was positive in five of six (83%) precursor B-lymphoblastic lymphoma, 11 of 37 (30%) chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/ SLL), five of 39 (13%) mantle cell lymphoma, one of 12 (8%) Burkitt lymphoma, and one of 12 (8%) nodal marginal zone B-cell lymphoma. In 22 cases of CLL/SLL, seven of nine (78%) with unmutated IgV H genes expressed ZAP-70, compared with one of 13 (8%) with mutated IgV H genes (P ¼ 0.0015 Fisher's exact test). ZAP-70 expression was not detected in diffuse large B-cell lymphoma (n ¼ 26), extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue (n ¼ 24), follicular lymphoma (n ¼ 21), plasma cell myeloma/ plasmacytoma (n ¼ 10), lymphoplasmacytic lymphoma (n ¼ 10), or splenic marginal zone lymphoma (n ¼ 6). In T/NK-cell NHL, ZAP-70 was positive in all extranodal natural killer (NK) / T-cell lymphoma, nasal-type (n ¼ 6) and enteropathy-type T-cell lymphoma (n ¼ 4), four of five (80%) subcutaneous panniculitis-like T-cell lymphoma, six of eight (75%) mycosis fungoides, three of five (60%) precursor T-lymphoblastic lymphoma, 10 of 17 (59%) peripheral T-cell lymphoma, two of four (50%) blastic NK-cell lymphoma, one of three (33%) T-cell prolymphocytic leukemia, 13 of 52 (25%) anaplastic large cell lymphoma, and one of six (17%) angioimmunoblastic T-cell lymphoma. Seven of 12 (58%) cutaneous CD30-positive lymphoproliferative disorders were also ZAP-70-positive. In Hodgkin lymphoma, ZAP-70 was negative in neoplastic cells in all cases tested. ZAP-70 staining in B-cell lymphomas and reactive T cells was predominantly nuclear with variable cytoplasmic staining. By contrast, ZAP-70 staining in T/NK-cell lymphomas was heterogeneous, and a shift from predominantly nuclear to predominantly cytoplasmic staining was observed, particularly in those neoplasms with high-grade morphology. In summary, ZAP-70 is expressed by many lymphoma types, correlates with immunoglobulin heavy-chain variable region gene mutational status in CLL/SLL, and can be detected reliably using immunohistochemical methods.

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Section: Zap-70 In Hodgkin Lymphomasmentioning

confidence: 93%

Immunohistochemical detection of ZAP-70 in 341 cases of non-Hodgkin and Hodgkin lymphoma

et al. 2004

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“…ZAP-70 had previously been discovered as a tyrosine kinase essential for T-cell receptor signal transduction. In addition to CLL, ZAP-70 expression has been reported in various B-cell malignancies and recently in human tonsillar B-cells as well (12,13). Importantly, CLL cells expressing ZAP-70 have been shown to be more responsive to B-cell receptor stimulation in vitro than CLL cells without ZAP-70, indicating that ZAP-70 could enhance B-cell receptor signaling for survival and proliferation and thereby contribute to disease progression (14).…”

Section: Zap-70 a Prognostic Markermentioning

confidence: 99%

Flow cytometry for ZAP‐70: New colors for chronic lymphocytic leukemia

Wiestner

2006

Cytometry Part B Clinical

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“…11 In addition, ZAP-70 has been reported to be expressed in a variable number of other mature and immature human B-lymphoid malignancies. [12][13][14][15] In this work, we have studied by Western blot (WB), flow cytometry (FC) and immunohistochemistry normal and malignant human B-cell subpopulations. We demonstrate that different subsets of human mature B lymphocytes express ZAP-70, regardless their tissue of origin or activation status, and with differences in terms of intensity of expression.…”

Section: Introductionmentioning

confidence: 99%

ZAP-70 is expressed by normal and malignant human B-cell subsets of different maturational stage

et al. 2006

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ZAP-70 tyrosine kinase is involved in signalling pathways following T-cell receptor stimulation and was originally described only in T cells and natural killer cells. ZAP-70 expression has been reported in normal mouse B lineage cells and in human malignant B lymphocytes, mainly in chronic lymphocytic leukemia (CLL) where it correlates with clinical outcome. We analyzed several B-cell lines and ex vivo malignant B cells, ranging from acute lymphoblastic leukemia to multiple myeloma and reflecting different stages of B-cell differentiation, and they showed ZAP-70 expression regardless their maturation stage. We then analyzed by Western blot and flow cytometry different human normal B-lymphocyte subpopulations: naïve, germinal center and memory B cells from tonsils, CD19 þ CD5 þ cells from cord blood and CD19 þ lymphocytes from peripheral blood. All expressed ZAP-70 protein, though at different levels depending on their differentiation, activation and tissue localization. In addition, ZAP-70 expression levels could be modulated following stimulation via the B-cell receptor. These findings implicate a potential role of ZAP-70 in the signalling pathway of B lymphocytes at different maturational stages, indicate that 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.

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ZAP-70 Expression in B-Cell Hematologic Malignancy Is Not Limited to CLL/SLL

Cited by 24 publications

References 16 publications

Immunohistochemical detection of ZAP-70 in 341 cases of non-Hodgkin and Hodgkin lymphoma

Immunohistochemical detection of ZAP-70 in 341 cases of non-Hodgkin and Hodgkin lymphoma

Flow cytometry for ZAP‐70: New colors for chronic lymphocytic leukemia

ZAP-70 is expressed by normal and malignant human B-cell subsets of different maturational stage

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