ZAP-70 upregulation in transformed B cells after early pre-BI cell transplant into NOD/SCID mice.
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.
Ruiz-Vela
Antonio
A
Department of Immunology and Oncology, Centro Nacional de Biotecnología/CSIC, Universidad Autónoma de Madrid, Campus de Cantoblanco, E-28049 Madrid, Spain.
Piqueras
Raquel
R
Carvalho-Pinto
Carla
C
Gómez
Lucio
L
Yaniz-Galende
Elisa
E
Moreno-Ortiz
Mari Carmen
MC
Bernad
Antonio
A
Harshman
Keith
K
Martínez-A
Carlos
C
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
D011505:Protein-Tyrosine Kinases; D051746:ZAP-70 Protein-Tyrosine Kinase; C497261:ZAP70 protein, human; C497262:Zap70 protein, mouse