ZAP-70 Upregulation

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Medline Abstract

Ruiz-Vela, Raquel Piqueras, Carla Carvalho-Pinto, Lucio

Gomez, Yaniz-Galende, Mari Carmen Moreno-Ortiz, Bernad,

Harshman, and ez-A

ZAP-70 upregulation in transformed B cells after early pre-BI cell

transplant into NOD/SCID mice.

Oncogene, April 18, 2005; .

1Department of Immunology and Oncology, Centro Nacional de

Biotecnología/CSIC, Universidad Autónoma de Madrid, Campus de

Cantoblanco, E-28049 Madrid, Spain.

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.Oncogene advance online publication, 18

April 2005; doi:10.1038/sj.onc.1208706.

PMID: 15856008