{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T00:42:34Z","timestamp":1790901754290,"version":"4.1.0"},"reference-count":73,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2005,11,8]],"date-time":"2005-11-08T00:00:00Z","timestamp":1131408000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Br J Haematol"],"published-print":{"date-parts":[[2006,1]]},"abstract":"<jats:title>Summary<\/jats:title><jats:p>The <jats:italic>TLX1<\/jats:italic>\/<jats:italic>HOX11<\/jats:italic> homeobox gene is frequently activated in T\u2010cell acute lymphoblastic leukaemia (T\u2010ALL) by the t(10;14)(q24;q11) and t(7;10)(q35;q24) chromosomal translocations or by as yet unknown transcriptional mechanisms in the absence of 10q24 cytogenetic abnormalities. Almost all TLX1<jats:sup>+<\/jats:sup> T\u2010ALLs exhibit a CD4<jats:sup>+<\/jats:sup>CD8<jats:sup>+<\/jats:sup> double\u2010positive (DP) phenotype. To investigate the role of <jats:italic>TLX1<\/jats:italic> as an initiating oncogene in T\u2010ALL pathogenesis, we assessed the consequences of retroviral vector\u2010directed <jats:italic>TLX1<\/jats:italic> expression during the differentiation of murine and human thymocytes in fetal thymic organ cultures. Interestingly, enforced expression of <jats:italic>TLX1<\/jats:italic> disrupted the differentiation of murine fetal liver precursors and human cord blood CD34<jats:sup>+<\/jats:sup> stem\/progenitor cells prior to the DP thymocyte stage. Although differentiation arrest was associated with an increased percentage of apoptotic thymocytes, it could only be partially bypassed by coexpression of transgenic <jats:italic>BCL2<\/jats:italic>. Mutation of the invariant asparagine residue at position 51 of the homeodomain \u2013 which is required for efficient DNA binding \u2013 released the block, consistent with the notion that TLX1 inhibits thymocyte differentiation and promotes T\u2010cell oncogenesis by functioning as a transcription factor. The relevance of these findings is discussed in the context of activating <jats:italic>NOTCH1<\/jats:italic> mutations and the other genetic lesions implicated in the multistep transformation process of TLX1<jats:sup>+<\/jats:sup> T\u2010ALL.<\/jats:p>","DOI":"10.1111\/j.1365-2141.2005.05850.x","type":"journal-article","created":{"date-parts":[[2005,11,8]],"date-time":"2005-11-08T15:56:30Z","timestamp":1131465390000},"page":"216-229","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":23,"title":["<i>TLX1<\/i>\/<i>HOX11<\/i>\u2010mediated disruption of primary thymocyte differentiation prior to the CD4<sup>+<\/sup>CD8<sup>+<\/sup> double\u2010positive stage"],"prefix":"10.1111","volume":"132","author":[{"given":"Bronwyn M.","family":"Owens","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Teresa S.","family":"Hawley","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lisa M.","family":"Spain","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kristi A.","family":"Kerkel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert G.","family":"Hawley","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2005,12,9]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.1021\/bi00044a040"},{"key":"e_1_2_6_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(00)80291-3"},{"key":"e_1_2_6_4_1","doi-asserted-by":"publisher","DOI":"10.3109\/10428190009065824"},{"key":"e_1_2_6_5_1","doi-asserted-by":"publisher","DOI":"10.1084\/jem.194.1.99"},{"key":"e_1_2_6_6_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2003-11-3944"},{"key":"e_1_2_6_7_1","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20040789"},{"key":"e_1_2_6_8_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.leu.2403061"},{"key":"e_1_2_6_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0952-7915(02)00322-9"},{"key":"e_1_2_6_10_1","doi-asserted-by":"crossref","first-page":"2180","DOI":"10.1182\/blood.V87.6.2180.bloodjournal8762180","article-title":"Multiple tumor\u2010suppressor gene 1 inactivation is the most frequent genetic alteration in T\u2010cell acute lymphoblastic leukemia","volume":"87","author":"Cayuela J.M.","year":"1996","journal-title":"Blood"},{"key":"e_1_2_6_11_1","doi-asserted-by":"publisher","DOI":"10.1038\/nri937"},{"key":"e_1_2_6_12_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.gt.3300507"},{"key":"e_1_2_6_13_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.172.9.5230"},{"key":"e_1_2_6_14_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.7569929"},{"key":"e_1_2_6_15_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2004-12-4897"},{"key":"e_1_2_6_16_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.169.6.3021"},{"key":"e_1_2_6_17_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.90.10.4431"},{"key":"e_1_2_6_18_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V78.11.2996.2996"},{"key":"e_1_2_6_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1535-6108(02)00018-1"},{"key":"e_1_2_6_20_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2003-07-2577"},{"key":"e_1_2_6_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(04)15542-6"},{"key":"e_1_2_6_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1074-7613(00)80053-9"},{"key":"e_1_2_6_23_1","doi-asserted-by":"crossref","first-page":"4244","DOI":"10.4049\/jimmunol.150.10.4244","article-title":"A developmental pathway involving four phenotypically and functionally distinct subsets of CD3\u2010CD4\u2010CD8\u2010 triple\u2010negative adult mouse thymocytes defined by CD44 and CD25 expression","volume":"150","author":"Godfrey D.I.","year":"1993","journal-title":"Journal of Immunology"},{"key":"e_1_2_6_24_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.leu.2403834"},{"key":"e_1_2_6_25_1","doi-asserted-by":"crossref","first-page":"83","DOI":"10.4049\/jimmunol.151.1.83","article-title":"bcl\u20102 proto\u2010oncogene expression during human T cell development. 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