{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,30]],"date-time":"2026-04-30T06:38:26Z","timestamp":1777531106604,"version":"3.51.4"},"reference-count":48,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2005,1,11]],"date-time":"2005-01-11T00:00:00Z","timestamp":1105401600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Intl Journal of Cancer"],"published-print":{"date-parts":[[2005,5,10]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>The <jats:italic>BCL\u20102<\/jats:italic> family has been implicated in the pathogenesis of various hematopoietic malignancies, including follicular non\u2010Hodgkin lymphoma and B\u2010cell chronic lymphocytic leukemia. To identify genes that act synergistically in BCL2\u2010enforced leukemogenesis, we developed a murine B\u2010cell lymphoma\/leukemia model based on the IL\u20103\u2010dependent Balb\/C pro\u2010B line (FL5.12). FL5.12 cells were stably transfected with antiapoptotic <jats:italic>BCL\u20102<\/jats:italic> alone or in combination with proapoptotic <jats:italic>BAX<\/jats:italic> or nonfunctional mutant <jats:italic>BAX<\/jats:italic>, thereby creating various levels of imbalance within the <jats:italic>BCL\u20102<\/jats:italic> family. Transfectants were intravenously injected into normal Balb\/C mice. Whereas FL5.12 cells did not provoke leukemia, mice injected with stable transfectants died of leukemia over time. Disease incidence and latency time depended on the degree of imbalance in the <jats:italic>BCL\u20102<\/jats:italic> family, supporting a model whereby BCL2 drives tumorigenesis. All mice presented with hepatosplenomegaly and leukemic FL5.12 cells in peripheral blood and bone marrow compartments. Leukemic conversion was accompanied by secondary genetic aberrations leading to clonal IL\u20103\u2010responsive leukemia. Cellular transformation was independent of alterations in <jats:italic>c\u2010Myc<\/jats:italic> or downstream apoptotic pathway. Leukemic clones retained a normal DNA damage response leading to elevated P53 and P21 levels and cell cycle arrest upon irradiation. In conclusion, our mouse model may prove a valuable tool to identify genes that cooperate in BCL2\u2010enforced lymphoma\/leukemogenesis. \u00a9 2004 Wiley\u2010Liss, Inc.<\/jats:p>","DOI":"10.1002\/ijc.20822","type":"journal-article","created":{"date-parts":[[2005,1,11]],"date-time":"2005-01-11T21:47:12Z","timestamp":1105480032000},"page":"917-925","source":"Crossref","is-referenced-by-count":19,"title":["Novel murine B\u2010cell lymphoma\/leukemia model to study BCL2\u2010driven oncogenesis"],"prefix":"10.1002","volume":"114","author":[{"given":"Jules P.P.","family":"Meijerink","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Esther M.M.","family":"Van Lieshout","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"H. 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