title: ZAP-70 upregulation in transformed B cells after early pre-BI cell transplant into NOD/SCID mice.
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.
authors.affiliation: Department of Immunology and Oncology, Centro Nacional de Biotecnología/CSIC, Universidad Autónoma de Madrid, Campus de Cantoblanco, E-28049 Madrid, Spain.
authors.forename: Antonio
authors.initials: A
authors.lastname: Ruiz-Vela
authors.forename: Raquel
authors.initials: R
authors.lastname: Piqueras
authors.forename: Carla
authors.initials: C
authors.lastname: Carvalho-Pinto
authors.forename: Lucio
authors.initials: L
authors.lastname: Gómez
authors.forename: Elisa
authors.initials: E
authors.lastname: Yaniz-Galende
authors.forename: Mari Carmen
authors.initials: MC
authors.lastname: Moreno-Ortiz
authors.forename: Antonio
authors.initials: A
authors.lastname: Bernad
authors.forename: Keith
authors.initials: K
authors.lastname: Harshman
authors.forename: Carlos
authors.initials: C
authors.lastname: Martínez-A
mesh_terms: D000818:Animals; D001402:B-Lymphocytes / Q000166:cytology / Q000502:physiology / Q000637:transplantation*; D002478:Cells, Cultured; D006801:Humans; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000235:genetics; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D011505:Protein-Tyrosine Kinases / Q000235:genetics*; D015398:Signal Transduction; D051746:ZAP-70 Protein-Tyrosine Kinase
chemical_list: D011505:Protein-Tyrosine Kinases; D051746:ZAP-70 Protein-Tyrosine Kinase; C497261:ZAP70 protein, human; C497262:Zap70 protein, mouse