title: Chimeric homeobox gene E2A-PBX1 induces proliferation, apoptosis, and malignant lymphomas in transgenic mice.
abstract: Expression of the homeobox fusion gene E2A-PBX1 under control of the immunoglobulin heavy chain enhancer efficiently induced malignancies in transgenic mice. All animals died before 5 months of age with lymphomas that demonstrated phenotypes consistent with transitional intermediate thymocytes (CD4+/CD8+/CD3med). E2A-PBX1 also markedly altered lymphoid development in pretumorous animals, reducing the number of thymocytes and bone marrow B lineage progenitors to 20% of normal levels. In spite of the observed reductions in lymphoid cells, premalignant animals contained significantly increased numbers of cycling thymocytes, but a higher proportion was also undergoing apoptosis, suggesting that increased cell death resulted in the marked lymphopenias. These data indicate that the chimeric homeodomain protein E2A-PBX1 paradoxically induces both proliferation and apoptosis in lymphoid cells, suggesting an in vivo association between nuclear oncogene-induced cell cycle progression and programed cell death.
authors.affiliation: Department of Pathology, Stanford University School of Medicine, California 94305.
authors.forename: D A
authors.initials: DA
authors.lastname: Dedera
authors.forename: E K
authors.initials: EK
authors.lastname: Waller
authors.forename: D P
authors.initials: DP
authors.lastname: LeBrun
authors.forename: A
authors.initials: A
authors.lastname: Sen-Majumdar
authors.forename: M E
authors.initials: ME
authors.lastname: Stevens
authors.forename: G S
authors.initials: GS
authors.lastname: Barsh
authors.forename: M L
authors.initials: ML
authors.lastname: Cleary
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal; D017209:Apoptosis / Q000235:genetics*; D017252:CD3 Complex / Q000032:analysis; D015704:CD4 Antigens / Q000032:analysis; D016827:CD8 Antigens / Q000032:analysis; D002453:Cell Cycle / Q000235:genetics; D002455:Cell Division / Q000235:genetics*; D002678:Chimera; D003001:Cloning, Molecular; D004742:Enhancer Elements, Genetic; D005801:Genes, Homeobox; D005822:Genetic Vectors; D006801:Humans; D007143:Immunoglobulin Heavy Chains / Q000235:genetics; D008223:Lymphoma / Q000235:genetics* / Q000276:immunology / Q000473:pathology; D051379:Mice; D008822:Mice, Transgenic; D016176:T-Lymphocyte Subsets / Q000276:immunology; D013950:Thymus Gland / Q000276:immunology / Q000473:pathology; D013953:Thymus Neoplasms / Q000235:genetics* / Q000276:immunology / Q000473:pathology; D014407:Tumor Cells, Cultured
chemical_list: D000911:Antibodies, Monoclonal; D017252:CD3 Complex; D015704:CD4 Antigens; D016827:CD8 Antigens; D007143:Immunoglobulin Heavy Chains