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Chronic Lymphocytic Leukemia, Normal B and T Cells

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

Leukemia volume 20, pages 689–695 (2006)Cite this article

Abstract

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+ CD5+ cells from cord blood and CD19+ 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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Acknowledgements

CS is a recipient of a scholarship from FIRC, Milano. We are grateful to Ms Rose Mary Carletti for her precious technical assistance and to Dr Michela Frenquelli for her continuous support in the lab work. We are indebted with Alessandro Ambrosi, Eliana La Ferrara e Giuseppe Guida for their precious advice on statistical analysis. This work was supported in part by Associazione Italiana per la Ricerca sul Cancro (AIRC), Progetto Oncologia CNR-MIUR, MURST 40%, the CLL Global Research Foundation, Ministero della Sanità (R.F.2002, no. 183), Fondazione CARIPLO and MIUR-Firb (RBNE01LNX7-006).

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Author notes

  1. C Scielzo and A Camporeale: These authors contributed equally to this work.

Authors and Affiliations

  1. Department of Oncology, Università Vita Salute – San Raffaele, Milan, Italy

    C Scielzo, A Camporeale, F Caligaris-Cappio & P Ghia

  2. Laboratory of Cancer Immunology, IRCC, Candiolo (TO), Italy

    M Geuna

  3. Proteome Biochemistry, San Raffaele Scientific Institute, Milan, Italy

    M Alessio

  4. Laboratory of Experimental Oncology D, National Institute for Cancer Research, Genoa, Italy

    A Poggi

  5. Laboratory of Tumor Immunology, San Raffaele Scientific Institute, Milan, Italy

    M R Zocchi

  6. Department of Internal Medicine, Clinical Hematology, University of Genoa, Genoa, Italy

    M R Zocchi

  7. Department of Pathology, University of Verona, Policlinico Borgo Roma, Verona, Italy

    M Chilosi

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  1. C Scielzo
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Correspondence to P Ghia.

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Scielzo, C., Camporeale, A., Geuna, M. et al. ZAP-70 is expressed by normal and malignant human B-cell subsets of different maturational stage. Leukemia 20, 689–695 (2006). https://doi.org/10.1038/sj.leu.2404138

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  • DOI: https://doi.org/10.1038/sj.leu.2404138

Keywords

  • ZAP-70
  • B lymphocytes
  • B-lymphoid malignancies
  • chronic lymphocytic leukemia

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