{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T00:33:26Z","timestamp":1791160406869,"version":"4.1.0"},"reference-count":30,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2013,6,17]],"date-time":"2013-06-17T00:00:00Z","timestamp":1371427200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancer Science"],"published-print":{"date-parts":[[2013,8]]},"abstract":"Bcl11b is a haploinsufficient tumor suppressor, mutations or deletion of which has been found in 10\u201316% of T\u2010cell acute lymphoblastic leukemias. Bcl11b<\/jats:italic>KO<\/jats:sup><\/jats:styled-content>\/+<\/jats:sup> heterozygous mice are susceptible to thymic lymphomas, a model of T\u2010cell acute lymphoblastic leukemia, when \u03b3\u2010irradiated, and irradiated Bcl11b<\/jats:italic>KO<\/jats:sup><\/jats:styled-content>\/+<\/jats:sup> mice generate clonally expanding or premalignant thymocytes before thymic lymphoma development. Cells with radiation\u2010induced DNA<\/jats:styled-content> damages are assumed to be the cells of origin in tumors; however, which thymocyte is the tumor cell origin remains obscure. In this study we generated Bcl11b<\/jats:italic><\/jats:styled-content>flox\/+<\/jats:sup>;Lck\u2010Cre<\/jats:italic><\/jats:styled-content> and Bcl11b<\/jats:italic><\/jats:styled-content>flox\/+<\/jats:sup>;CD4\u2010Cre<\/jats:italic><\/jats:styled-content> mice; in the former, loss of one Bcl11b<\/jats:italic><\/jats:styled-content> allele occurs in thymocytes at the immature CD<\/jats:styled-content>4\u2212<\/jats:sup>CD<\/jats:styled-content>8\u2212<\/jats:sup> stage, whereas in the latter the loss occurs in the more differentiated CD<\/jats:styled-content>4+<\/jats:sup>CD<\/jats:styled-content>8+<\/jats:sup> double\u2010positive stage. We examined clonal expansion and differentiation of thymocytes in mice 60\u00a0days after 3\u00a0Gy \u03b3\u2010irradiation. Half (9\/18) of the thymuses in the Bcl11b<\/jats:italic><\/jats:styled-content>flox\/+<\/jats:sup>;Lck\u2010Cre<\/jats:italic><\/jats:styled-content> group showed limited rearrangement sites at the T\u2010cell receptor\u2010\u03b2 (TCR\u03b2<\/jats:italic><\/jats:styled-content>) locus, indicating clonal cell expansion, but none in the Bcl11b<\/jats:italic><\/jats:styled-content>flox\/+<\/jats:sup>;CD4\u2010Cre<\/jats:italic><\/jats:styled-content> group did. This indicates that the origin of the premalignant thymocytes is not in double\u2010positive cells but immature thymocytes. Interestingly, those premalignant thymocytes underwent rearrangement at various different sites of the TCR\u03b1<\/jats:italic><\/jats:styled-content> locus and the majority showed a higher expression of TCR<\/jats:styled-content>\u03b2 and CD<\/jats:styled-content>8, and more differentiated phenotypes. This suggests the existence of a subpopulation of immature cells within the premalignant cells that is capable of proliferating and continuously producing differentiated thymocytes.<\/jats:p>","DOI":"10.1111\/cas.12193","type":"journal-article","created":{"date-parts":[[2013,5,13]],"date-time":"2013-05-13T07:22:37Z","timestamp":1368429757000},"page":"1009-1016","source":"Crossref","is-referenced-by-count":7,"title":["Cell of origin in radiation\u2010induced premalignant thymocytes with differentiation capability in mice conditionally losing one Bcl11b<\/i><\/scp> allele"],"prefix":"10.1111","volume":"104","author":[{"given":"Rieka","family":"Go","sequence":"first","affiliation":[{"name":"Department of Molecular Genetics Graduate School of Medical and Dental Sciences Niigata Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Satoshi","family":"Hirose","sequence":"additional","affiliation":[{"name":"Department of Molecular Genetics Graduate School of Medical and Dental Sciences Niigata Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoshinori","family":"Katsuragi","sequence":"additional","affiliation":[{"name":"Department of Molecular Genetics Graduate School of Medical and Dental Sciences Niigata Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Miki","family":"Obata","sequence":"additional","affiliation":[{"name":"Department of Molecular Genetics Graduate School of Medical and Dental Sciences Niigata Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manabu","family":"Abe","sequence":"additional","affiliation":[{"name":"Brain Research Institute, Niigata University Niigata Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yukio","family":"Mishima","sequence":"additional","affiliation":[{"name":"Department of Molecular Genetics Graduate School of Medical and Dental Sciences Niigata Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kenji","family":"Sakimura","sequence":"additional","affiliation":[{"name":"Brain Research Institute, Niigata University Niigata Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ryo","family":"Kominami","sequence":"additional","affiliation":[{"name":"Department of Molecular Genetics Graduate School of Medical and Dental Sciences Niigata Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2013,6,17]]},"reference":[{"key":"e_1_2_7_2_1","first-page":"422","article-title":"Indirect induction of lymphomas in irradiated mice. 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