{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,31]],"date-time":"2025-10-31T13:57:16Z","timestamp":1761919036225},"reference-count":37,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2007,7,16]],"date-time":"2007-07-16T00:00:00Z","timestamp":1184544000000},"content-version":"vor","delay-in-days":45,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Annals of the New York Academy of Sciences"],"published-print":{"date-parts":[[2007,6]]},"abstract":"<jats:p><jats:bold><jats:sc>Abstract:\u2002<\/jats:sc><\/jats:bold>  <jats:bold>Insertion sites of replication\u2010deficient retroviral vectors may trigger clonal dominance of hematopoietic cells <jats:italic>in vivo<\/jats:italic>. Here, we tested whether this would also be the case when using vectors that express powerful oncogenes, such as the large tumor antigen (TAg) of simian virus 40. TAg inactivates the tumor\u2010suppressor proteins p53 and Rb by virtue of a chaperone\u2010like activity. Primary hematopoietic stem\/progenitor cells transduced with retroviral vectors encoding TAg\u2010induced histiocytic sarcoma (HS) or myeloid leukemia (ML) in transplanted mice (average survival of 21 weeks). Retrovirally introducing TAg into pretransformed 32D cells generated a monocytic leukemia, with faster kinetics (\u223c8 weeks). Leukemic clones showed retroviral insertions in genes contributing to all known TAg cooperation pathways, acting mitogenic and\/or modulating apoptosis (such as <jats:italic>BclX, Crk, Pim2, Csfr1\/Pdgfrb, Osm\/Lif, Axl, Fli, Sema4b, Sox4<\/jats:italic>). 32D\u2010derived monocytic leukemias showed hits in <jats:italic>Pim2<\/jats:italic> and <jats:italic>Max<\/jats:italic> proto\u2010oncogenes, or the chaperone <jats:italic>Hspa4,<\/jats:italic> plus additional signaling genes. Vector\u2010mediated insertional mutagenesis thus revealed a broad spectrum of potential TAg complementation genes. These findings have important implications for the use of retroviral transgenesis in cancer research, and the expression of signaling genes in somatic gene therapy.<\/jats:bold> <\/jats:p>","DOI":"10.1196\/annals.1392.003","type":"journal-article","created":{"date-parts":[[2007,7,19]],"date-time":"2007-07-19T19:28:24Z","timestamp":1184873304000},"page":"95-113","source":"Crossref","is-referenced-by-count":14,"title":["Insertional Mutagenesis by Replication\u2010Deficient Retroviral Vectors Encoding the Large T Oncogene"],"prefix":"10.1111","volume":"1106","author":[{"given":"ZHIXIONG","family":"LI","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"OLGA 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