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ZAP-70 upregulation in transformed B cells after early pre-BI cell transplant into NOD/SCID mice

Oncogene volume 24, pages 5119–5124 (2005)Cite this article

Abstract

Understanding of the signal transduction pathways that lead to B cell development is of extreme interest to learn how alterations in these pathways might initiate malignant transformation. Long-term cultured early pre-BI cells can differentiate into IgM+ B cells after transplant into NOD/SCID mice, offering the possibility to explore checkpoints in B cell development. Using DNA microarray and Western blot analysis of IgM+ B cells vs parental early pre-BI cells, we demonstrated that zeta-associated protein 70 (ZAP-70) is upregulated in our B cell differentiation model. Unlike parental ZAP-70− early pre-BI cells, ZAP-70+ IgM+ B cells exhibited a transformed phenotype, as indicated by BCL-6 expression, a high Ki-67 proliferation index, resistance to IL-7 deprivation-induced apoptosis, and an increased repopulation rate in NOD/SCID mice. These data show the characterization and generation of a novel murine leukemia model with many similarities to human ZAP-70+ B cell chronic lymphocytic leukemia.

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Acknowledgements

We thank the technical staff of the department who aid with cell culture and materials preparation, and C Mark for editorial assistance. The Department of Immunology and Oncology was founded and is supported by the Spanish National Research Council (CSIC) and by Pfizer.

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  1. Department of Immunology and Oncology, Centro Nacional de Biotecnología/CSIC, Universidad Autónoma de Madrid, Campus de Cantoblanco, Madrid, E-28049, Spain

    Antonio Ruiz-Vela, Raquel Piqueras, Carla Carvalho-Pinto, Lucio Gómez, Elisa Yaniz-Galende, Mari Carmen Moreno-Ortiz, Antonio Bernad, Keith Harshman & Carlos Martínez-A

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Correspondence to Antonio Ruiz-Vela.

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Ruiz-Vela, A., Piqueras, R., Carvalho-Pinto, C. et al. ZAP-70 upregulation in transformed B cells after early pre-BI cell transplant into NOD/SCID mice. Oncogene 24, 5119–5124 (2005). https://doi.org/10.1038/sj.onc.1208706

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