{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T14:17:58Z","timestamp":1791296278102,"version":"4.1.0"},"reference-count":47,"publisher":"National Academy of Sciences","issue":"16","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2004,4,20]]},"abstract":"<jats:p>\n                    Impaired apoptosis is now recognized to be central to tumor development. Bcl2, activated by chromosomal translocation in human follicular lymphoma, promotes oncogenesis by inhibiting apoptosis. Bim, a distant proapoptotic relative, is emerging as a major physiologic antagonist of Bcl2. Here, we show that loss of Bim is oncogenic. Bim protein levels were elevated in the apoptosis-prone B lymphoid cells of E\u03bc-\n                    <jats:italic>Myc<\/jats:italic>\n                    -transgenic mice, and\n                    <jats:italic>Bim<\/jats:italic>\n                    -mutant E\u03bc-\n                    <jats:italic>Myc<\/jats:italic>\n                    mice had increased numbers of IgM-bearing B cells. E\u03bc-\n                    <jats:italic>Myc<\/jats:italic>\n                    -expressing B lymphoid cells deficient in Bim were refractory to apoptosis induced\n                    <jats:italic>in vitro<\/jats:italic>\n                    by cytokine deprivation or antigen receptor cross-linking. Thus, Bim is induced by Myc in B cells and mediates apoptosis. Remarkably, inactivation of even a single allele of\n                    <jats:italic>Bim<\/jats:italic>\n                    accelerated Myc-induced development of tumors, particularly acute B cell leukemia. None of the primary tumors from\n                    <jats:italic>Bim<\/jats:italic>\n                    <jats:sup>+\/-<\/jats:sup>\n                    E\u03bc-\n                    <jats:italic>Myc<\/jats:italic>\n                    mice displayed loss of the second allele of\n                    <jats:italic>Bim<\/jats:italic>\n                    . These findings indicate that Bim is a tumor suppressor, at least in B lymphocytes, and is haploinsufficient. Whereas the p19Arf\/p53 pathway is frequently mutated in tumors arising in\n                    <jats:italic>Bim<\/jats:italic>\n                    <jats:sup>\n                      +\n                      <jats:italic>\/<\/jats:italic>\n                      +\n                    <\/jats:sup>\n                    E\u03bc-\n                    <jats:italic>Myc<\/jats:italic>\n                    mice, it was unaffected in most Bim-deficient tumors, indicating that Bim reduction is an effective alternative to loss of p53 function.\n                  <\/jats:p>","DOI":"10.1073\/pnas.0401471101","type":"journal-article","created":{"date-parts":[[2004,4,12]],"date-time":"2004-04-12T21:04:03Z","timestamp":1081803843000},"page":"6164-6169","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":423,"title":["Bim is a suppressor of Myc-induced mouse B cell leukemia"],"prefix":"10.1073","volume":"101","author":[{"given":"Alexander","family":"Egle","sequence":"first","affiliation":[{"name":"The Walter and Eliza Hall Institute of Medical Research, 1G Royal Parade, Melbourne, Victoria 3050, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alan W.","family":"Harris","sequence":"additional","affiliation":[{"name":"The Walter and Eliza Hall Institute of Medical Research, 1G Royal Parade, Melbourne, Victoria 3050, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Philippe","family":"Bouillet","sequence":"additional","affiliation":[{"name":"The Walter and Eliza Hall Institute of Medical Research, 1G Royal Parade, Melbourne, Victoria 3050, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Suzanne","family":"Cory","sequence":"additional","affiliation":[{"name":"The Walter and Eliza Hall Institute of Medical Research, 1G Royal Parade, Melbourne, Victoria 3050, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2004,4,12]]},"reference":[{"key":"e_1_3_2_1_2","first-page":"1685s","volume":"59","year":"1999","unstructured":"Cory, S., Vaux, D. 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