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In the present report we show that T-cell leukemic cells from E\u03bcSR\u03b1-TEL-JAK2 transgenic mice present an aberrant CD8+ differentiation phenotype, as determined by the expression of stage-specific cell surface markers and lineage-specific genes. TEL-JAK2 transforms immature CD4\u2212CD8\u2212 double-negative thymocytes, as demonstrated by the development of T-cell leukemia with full penetrance in a Rag2-deficient genetic background. This disease is similar to the bona fide TEL-JAK2 disease as assessed by phenotypic and gene profiling analyses. Pre-TCR signaling synergizes with TEL-JAK2 to transform immature thymocytes and initiate leukemogenesis as shown by (1) the delayed leukemia onset in Rag2-, CD3\u03f5- and pT\u03b1-deficient mice, (2) the occurrence of recurrent chromosomal alterations in pre-TCR\u2013deficient leukemia, and (3) the correction of delayed leukemia onset in Rag2-deficient TEL-JAK2 mice by an H-Y TCR\u03b1\u03b2 transgene that mimics pre-TCR signaling. Although not affecting leukemia incidence and mouse survival, TCR\u03b1\u03b2 expression was shown to facilitate leukemic cell expansion in secondary lymphoid organs.<\/jats:p>","DOI":"10.1182\/blood-2006-09-048801","type":"journal-article","created":{"date-parts":[[2006,12,27]],"date-time":"2006-12-27T20:14:11Z","timestamp":1167250451000},"page":"3972-3981","update-policy":"https:\/\/doi.org\/10.1182\/blood.2019cm0000","source":"Crossref","is-referenced-by-count":38,"title":["Pre-TCR expression cooperates with TEL-JAK2 to transform immature thymocytes and induce T-cell leukemia"],"prefix":"10.1182","volume":"109","author":[{"given":"Nuno R.","family":"dos Santos","sequence":"first","affiliation":[{"name":"Institut Curie, Centre de Recherche, Orsay, France;"},{"name":"CNRS UMR146, Orsay, France;"}]},{"given":"David S.","family":"Rickman","sequence":"additional","affiliation":[{"name":"Programme Cartes d'Identite\u0301 des Tumeurs (CIT), Ligue Nationale Contre Le Cancer, Paris, France;"}]},{"given":"Aure\u0301lien","family":"de Reynies","sequence":"additional","affiliation":[{"name":"Programme Cartes d'Identite\u0301 des Tumeurs (CIT), Ligue Nationale Contre Le Cancer, Paris, France;"}]},{"given":"Franc\u0327oise","family":"Cormier","sequence":"additional","affiliation":[{"name":"Institut Curie, Centre de Recherche, Orsay, France;"},{"name":"CNRS UMR146, Orsay, France;"}]},{"given":"Maryvonne","family":"Williame","sequence":"additional","affiliation":[{"name":"Institut Curie, Centre de Recherche, Orsay, France;"},{"name":"CNRS UMR146, Orsay, France;"}]},{"given":"Camille","family":"Blanchard","sequence":"additional","affiliation":[{"name":"Institut Curie, Centre de Recherche, Paris, France;"},{"name":"INSERM U509, Paris, France"}]},{"given":"Marc-Henri","family":"Stern","sequence":"additional","affiliation":[{"name":"Institut Curie, Centre de Recherche, Paris, France;"},{"name":"INSERM U509, Paris, France"}]},{"given":"Jacques","family":"Ghysdael","sequence":"additional","affiliation":[{"name":"Institut Curie, Centre de Recherche, Orsay, France;"},{"name":"CNRS UMR146, Orsay, France;"}]}],"member":"234","published-online":{"date-parts":[[2006,12,27]]},"reference":[{"key":"2019111713155064500_B1","doi-asserted-by":"crossref","unstructured":"Aifantis I, Mandal M, Sawai K, Ferrando A, Vilimas T. 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