title: Human HMGA2 protein overexpressed in mice induces precursor T-cell lymphoblastic leukemia.
abstract: T-cell acute lymphoblastic leukemia (T-ALL) is a neoplasia of thymocytes characterized by the rapid accumulation of the precursors of T lymphocytes. HMGA2 (high-mobility group AT-hook 2) gene expression is extremely low in normal adult tissues, but it is overexpressed in many tumors. To identify the biological function of HMGA2, we generated transgenic mice carrying the human HMGA2 gene under control of the VH promoter/Eμ enhancer. Approximately 90% of Eμ-HMGA2 transgenic mice became visibly sick between 4 and 8 months due to the onset and progression of a T-ALL-like disease. Characteristic features included severe alopecia (30% of mice); enlarged lymph nodes and spleen; and profound immunological abnormalities (altered cytokine levels, hypoimmunoglobulinemia) leading to reduced immune responsiveness. Immunophenotyping showed accumulation of CD5+CD4+, CD5+CD8+ or CD5+CD8+CD4+ T-cell populations in the spleens and bone marrow of sick animals. These findings show that HMGA2-driven leukemia in mice closely resembles spontaneous human T-ALL, indicating that HMGA2 transgenic mice should serve as an important model for investigating basic mechanisms and potential new therapies of relevance to human T-ALL.
authors.affiliation: Division of Hematology, College of Medicine, Comprehensive Cancer Center, The Ohio State University, Columbus, OH, USA.
authors.forename: A
authors.initials: A
authors.lastname: Efanov
authors.affiliation: Department of Molecular Virology, Immunology and Medical Genetics, Human Cancer Genetics Program, Comprehensive Cancer Center, OSU School of Medicine, The Ohio State University, Columbus, OH, USA.
authors.forename: N
authors.initials: N
authors.lastname: Zanesi
authors.affiliation: Department of Molecular Virology, Immunology and Medical Genetics, Human Cancer Genetics Program, Comprehensive Cancer Center, OSU School of Medicine, The Ohio State University, Columbus, OH, USA.
authors.forename: V
authors.initials: V
authors.lastname: Coppola
authors.affiliation: 1] Department of Pathology, Human Cancer Genetics Program, Comprehensive Cancer Center, OSU School of Medicine, The Ohio State University, Columbus, OH, USA [2] Phylogeny Laboratory, Columbus, OH, USA.
authors.forename: G
authors.initials: G
authors.lastname: Nuovo
authors.affiliation: Department of Veterinary Biosciences, Comparative Pathology and Mouse Phenotyping Shared Resource, Comprehensive Cancer Center, The Ohio State University, Columbus, OH, USA.
authors.forename: B
authors.initials: B
authors.lastname: Bolon
authors.affiliation: Department of Molecular Virology, Immunology and Medical Genetics, Human Cancer Genetics Program, Comprehensive Cancer Center, OSU School of Medicine, The Ohio State University, Columbus, OH, USA.
authors.forename: D
authors.initials: D
authors.lastname: Wernicle-Jameson
authors.affiliation: Division of Hematology, College of Medicine, Comprehensive Cancer Center, The Ohio State University, Columbus, OH, USA.
authors.forename: A
authors.initials: A
authors.lastname: Lagana
authors.affiliation: Division of Hematology, College of Medicine, Comprehensive Cancer Center, The Ohio State University, Columbus, OH, USA.
authors.forename: A
authors.initials: A
authors.lastname: Hansjuerg
authors.affiliation: Division of Hematology, College of Medicine, Comprehensive Cancer Center, The Ohio State University, Columbus, OH, USA.
authors.forename: F
authors.initials: F
authors.lastname: Pichiorri
authors.affiliation: Department of Molecular Virology, Immunology and Medical Genetics, Human Cancer Genetics Program, Comprehensive Cancer Center, OSU School of Medicine, The Ohio State University, Columbus, OH, USA.
authors.forename: C M
authors.initials: CM
authors.lastname: Croce
mesh_terms: D000818:Animals; D049109:Cell Proliferation / Q000502:physiology; D005260:Female; D025743:HMGA2 Protein / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism; D006801:Humans; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D010641:Phenotype; D054218:Precursor T-Cell Lymphoblastic Leukemia-Lymphoma / Q000235:genetics / Q000378:metabolism* / Q000473:pathology
chemical_list: D025743:HMGA2 Protein