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To identify the biological function of HMGA2, we generated transgenic mice carrying the human <jats:italic>HMGA2<\/jats:italic> gene under control of the V<jats:sub>H<\/jats:sub> promoter\/E\u03bc enhancer. Approximately 90% of E\u03bc-<jats:italic>HMGA2<\/jats:italic> 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 <jats:italic>HMGA2<\/jats:italic> transgenic mice should serve as an important model for investigating basic mechanisms and potential new therapies of relevance to human T-ALL.<\/jats:p>","DOI":"10.1038\/bcj.2014.46","type":"journal-article","created":{"date-parts":[[2014,7,11]],"date-time":"2014-07-11T13:18:22Z","timestamp":1405084702000},"page":"e227-e227","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":20,"title":["Human HMGA2 protein overexpressed in mice induces precursor T-cell lymphoblastic leukemia"],"prefix":"10.1038","volume":"4","author":[{"given":"A","family":"Efanov","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"N","family":"Zanesi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"V","family":"Coppola","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"G","family":"Nuovo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"B","family":"Bolon","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"D","family":"Wernicle-Jameson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A","family":"Lagana","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A","family":"Hansjuerg","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"F","family":"Pichiorri","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C M","family":"Croce","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2014,7,11]]},"reference":[{"key":"BFbcj201446_CR1","doi-asserted-by":"publisher","first-page":"3398","DOI":"10.1172\/JCI61269","volume":"122","author":"P Vlierberghe","year":"2012","unstructured":"Vlierberghe P, Ferrando A . 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