{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,8,7]],"date-time":"2025-08-07T08:57:44Z","timestamp":1754557064858},"reference-count":75,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2009,10,27]],"date-time":"2009-10-27T00:00:00Z","timestamp":1256601600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genes Chromosomes &amp; Cancer"],"published-print":{"date-parts":[[2010,2]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Translocations resulting in ectopic expression of the<jats:italic>TLX1<\/jats:italic>homeobox gene (previously known as<jats:italic>HOX11<\/jats:italic>) are recurrent events in human T\u2010cell acute lymphoblastic leukemia (T\u2010ALL). Transduction of primary murine hematopoietic stem\/progenitor cells with retroviral vectors expressing<jats:italic>TLX1<\/jats:italic>readily yields immortalized hematopoietic progenitor cell lines. Understanding the processes involved in<jats:italic>TLX1<\/jats:italic>\u2010mediated cellular immortalization should yield insights into the growth and differentiation pathways altered by<jats:italic>TLX1<\/jats:italic>during the development of T\u2010ALL. In recent clinical gene therapy trials, hematopoietic clonal dominance or T\u2010ALL\u2010like diseases have occurred as a direct consequence of insertional activation of the<jats:italic>EVI1<\/jats:italic>,<jats:italic>PRDM16<\/jats:italic>or<jats:italic>LMO2<\/jats:italic>proto\u2010oncogenes by the retroviral vectors used to deliver the therapeutic genes. Additionally, the generation of murine hematopoietic progenitor cell lines due to retroviral integrations into<jats:italic>Evi1<\/jats:italic>or<jats:italic>Prdm16<\/jats:italic>has also been recently reported. Here, we determined by linker\u2010mediated nested polymerase chain reaction the integration sites in eight<jats:italic>TLX1<\/jats:italic>\u2010immortalized hematopoietic cell lines. Notably, no common integration site was observed among the cell lines. Moreover, no insertions into the<jats:italic>Evi1<\/jats:italic>or<jats:italic>Prdm16<\/jats:italic>genes were identified although insertion near<jats:italic>Lmo2<\/jats:italic>was observed in one instance. However, neither<jats:italic>Lmo2<\/jats:italic>nor any of the other genes examined surrounding the integration sites showed differential vector\u2010influenced expression compared to the cell lines lacking such insertions. While we cannot exclude the possibility that insertional side effects transiently provided a selective growth\/survival advantage to the hematopoietic progenitor populations, our results unequivocally rule out insertions into<jats:italic>Evi1<\/jats:italic>and<jats:italic>Prdm16<\/jats:italic>as being integral to the<jats:italic>TLX1<\/jats:italic>\u2010initiated immortalization process. \u00a9 2009 Wiley\u2010Liss, Inc.<\/jats:p>","DOI":"10.1002\/gcc.20725","type":"journal-article","created":{"date-parts":[[2009,10,27]],"date-time":"2009-10-27T20:43:30Z","timestamp":1256676210000},"page":"119-131","source":"Crossref","is-referenced-by-count":2,"title":["Hematopoietic immortalizing function of the NKL\u2010subclass homeobox gene<i>TLX1<\/i>"],"prefix":"10.1002","volume":"49","author":[{"given":"Lynnsey A.","family":"Zweier\u2010Renn","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Teresa 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