{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T13:37:53Z","timestamp":1790775473314,"version":"4.1.0"},"reference-count":55,"publisher":"Rockefeller University Press","issue":"1","content-domain":{"domain":["rupress.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2005,7,4]]},"abstract":"<jats:p>CCAAT\/enhancer binding protein (C\/EBP)\u03b1 is a myeloid-specific transcription factor that couples lineage commitment to terminal differentiation and cell cycle arrest, and is found mutated in 9% of patients who have acute myeloid leukemia (AML). We previously showed that mutations which dissociate the ability of C\/EBP\u03b1 to block cell cycle progression through E2F inhibition from its function as a transcriptional activator impair the in vivo development of the neutrophil granulocyte and adipose lineages. We now show that such mutations increase the capacity of bone marrow (BM) myeloid progenitors to proliferate, and predispose mice to a granulocytic myeloproliferative disorder and transformation of the myeloid compartment of the BM. Both of these phenotypes were transplantable into lethally irradiated recipients. BM transformation was characterized by a block in granulocyte differentiation, accumulation of myeloblasts and promyelocytes, and expansion of myeloid progenitor populations\u2014all characteristics of AML. Circulating myeloblasts and hepatic leukocyte infiltration were observed, but thrombocytopenia, anemia, and elevated leukocyte count\u2014normally associated with AML\u2014were absent. These results show that disrupting the cell cycle regulatory function of C\/EBP\u03b1 is sufficient to initiate AML-like transformation of the granulocytic lineage, but only partially the peripheral pathology of AML.<\/jats:p>","DOI":"10.1084\/jem.20050067","type":"journal-article","created":{"date-parts":[[2005,6,27]],"date-time":"2005-06-27T20:25:55Z","timestamp":1119903955000},"page":"85-96","update-policy":"https:\/\/doi.org\/10.1084\/jem.crossmarkpolicy","source":"Crossref","is-referenced-by-count":109,"title":["Loss of C\/EBP\u03b1 cell cycle control increases myeloid progenitor proliferation and transforms the neutrophil granulocyte lineage"],"prefix":"10.1084","volume":"202","author":[{"given":"Bo T.","family":"Porse","sequence":"first","affiliation":[{"name":"1Laboratory of Gene Therapy Research, Copenhagen University Hospital, 2100 Copenhagen, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Bryder","sequence":"additional","affiliation":[{"name":"3Department of Stem Cell Biology, Hematopoietic Stem Cell Laboratory, Lund Strategic Research Center for Stem Cell Biology and Cell Therapy, Lund University, 22184 Lund, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kim","family":"Theilgaard-Mo\u0308nch","sequence":"additional","affiliation":[{"name":"2Granulocyte Laboratory, Copenhagen University Hospital, 2100 Copenhagen, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marie S.","family":"Hasemann","sequence":"additional","affiliation":[{"name":"1Laboratory of Gene Therapy Research, Copenhagen University Hospital, 2100 Copenhagen, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kristina","family":"Anderson","sequence":"additional","affiliation":[{"name":"3Department of Stem Cell Biology, Hematopoietic Stem Cell Laboratory, Lund Strategic Research Center for Stem Cell Biology and Cell Therapy, Lund University, 22184 Lund, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Inge","family":"Damgaard","sequence":"additional","affiliation":[{"name":"1Laboratory of Gene Therapy Research, Copenhagen University Hospital, 2100 Copenhagen, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sten Eirik W.","family":"Jacobsen","sequence":"additional","affiliation":[{"name":"3Department of Stem Cell Biology, Hematopoietic Stem Cell Laboratory, Lund Strategic Research Center for Stem Cell Biology and Cell Therapy, Lund University, 22184 Lund, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claus","family":"Nerlov","sequence":"additional","affiliation":[{"name":"1Laboratory of Gene Therapy Research, Copenhagen University Hospital, 2100 Copenhagen, Denmark"},{"name":"4EMBL Mouse Biology Unit, 00016 Monterotondo, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"291","published-online":{"date-parts":[[2005,6,27]]},"reference":[{"key":"2023072513224402200_BIB1","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1038\/35049577","volume":"1","year":"2000","journal-title":"Nat. Rev. Genet."},{"key":"2023072513224402200_BIB2","doi-asserted-by":"crossref","first-page":"569","DOI":"10.1073\/pnas.94.2.569","volume":"94","year":"1997","journal-title":"Proc. Natl. Acad. Sci. USA."},{"key":"2023072513224402200_BIB3","doi-asserted-by":"crossref","first-page":"1332","DOI":"10.1182\/blood.V99.4.1332","volume":"99","year":"2002","journal-title":"Blood."},{"key":"2023072513224402200_BIB4","doi-asserted-by":"crossref","first-page":"263","DOI":"10.1038\/85820","volume":"27","year":"2001","journal-title":"Nat. Genet."},{"key":"2023072513224402200_BIB5","doi-asserted-by":"crossref","first-page":"2717","DOI":"10.1182\/blood-2002-03-0990","volume":"100","year":"2002","journal-title":"Blood."},{"key":"2023072513224402200_BIB6","doi-asserted-by":"crossref","first-page":"343","DOI":"10.1038\/sj.leu.2402805","volume":"17","year":"2003","journal-title":"Leukemia."},{"key":"2023072513224402200_BIB7","doi-asserted-by":"crossref","first-page":"72","DOI":"10.1002\/gcc.10185","volume":"37","year":"2003","journal-title":"Genes Chromosomes Cancer."},{"key":"2023072513224402200_BIB8","doi-asserted-by":"crossref","first-page":"5647","DOI":"10.1002\/j.1460-2075.1996.tb00949.x","volume":"15","year":"1996","journal-title":"EMBO J."},{"key":"2023072513224402200_BIB9","doi-asserted-by":"crossref","first-page":"1573","DOI":"10.1126\/science.8079170","volume":"265","year":"1994","journal-title":"Science."},{"key":"2023072513224402200_BIB10","doi-asserted-by":"crossref","first-page":"998","DOI":"10.1182\/blood.V100.3.998","volume":"100","year":"2002","journal-title":"Blood."},{"key":"2023072513224402200_BIB11","doi-asserted-by":"crossref","first-page":"2403","DOI":"10.1101\/gad.12.15.2403","volume":"12","year":"1998","journal-title":"Genes Dev."},{"key":"2023072513224402200_BIB12","doi-asserted-by":"crossref","first-page":"148","DOI":"10.1038\/ng955","volume":"32","year":"2002","journal-title":"Nat. Genet."},{"key":"2023072513224402200_BIB13","doi-asserted-by":"crossref","first-page":"5506","DOI":"10.1128\/MCB.22.15.5506-5517.2002","volume":"22","year":"2002","journal-title":"Mol. Cell. Biol."},{"key":"2023072513224402200_BIB14","doi-asserted-by":"crossref","first-page":"444","DOI":"10.1038\/86515","volume":"7","year":"2001","journal-title":"Nat. Med."},{"key":"2023072513224402200_BIB15","doi-asserted-by":"crossref","first-page":"48","DOI":"10.1038\/ng791","volume":"30","year":"2002","journal-title":"Nat. Genet."},{"key":"2023072513224402200_BIB16","doi-asserted-by":"crossref","first-page":"270","DOI":"10.1182\/blood-2002-04-1288","volume":"101","year":"2003","journal-title":"Blood."},{"key":"2023072513224402200_BIB17","doi-asserted-by":"crossref","first-page":"322","DOI":"10.1128\/MCB.18.1.322","volume":"18","year":"1998","journal-title":"Mol. Cell. Biol."},{"key":"2023072513224402200_BIB18","doi-asserted-by":"crossref","first-page":"624","DOI":"10.1038\/ng1361","volume":"36","year":"2004","journal-title":"Nat. Genet."},{"key":"2023072513224402200_BIB19","doi-asserted-by":"crossref","first-page":"1108","DOI":"10.1126\/science.7652557","volume":"269","year":"1995","journal-title":"Science."},{"key":"2023072513224402200_BIB20","doi-asserted-by":"crossref","first-page":"804","DOI":"10.1101\/gad.10.7.804","volume":"10","year":"1996","journal-title":"Genes Dev."},{"key":"2023072513224402200_BIB21","doi-asserted-by":"crossref","first-page":"817","DOI":"10.1016\/S1097-2765(01)00366-5","volume":"8","year":"2001","journal-title":"Mol. Cell."},{"key":"2023072513224402200_BIB22","doi-asserted-by":"crossref","first-page":"5986","DOI":"10.1128\/MCB.20.16.5986-5997.2000","volume":"20","year":"2000","journal-title":"Mol. Cell. Biol."},{"key":"2023072513224402200_BIB23","doi-asserted-by":"crossref","first-page":"247","DOI":"10.1016\/S0092-8674(01)00516-5","volume":"107","year":"2001","journal-title":"Cell."},{"key":"2023072513224402200_BIB24","doi-asserted-by":"crossref","first-page":"3789","DOI":"10.1128\/MCB.21.11.3789-3806.2001","volume":"21","year":"2001","journal-title":"Mol. Cell. Biol."},{"key":"2023072513224402200_BIB25","doi-asserted-by":"crossref","first-page":"2548","DOI":"10.1038\/sj.onc.1206360","volume":"22","year":"2003","journal-title":"Oncogene."},{"key":"2023072513224402200_BIB26","doi-asserted-by":"crossref","first-page":"3163","DOI":"10.1182\/blood-2003-02-0479","volume":"102","year":"2003","journal-title":"Blood."},{"key":"2023072513224402200_BIB27","first-page":"59","volume":"9","year":"1998","journal-title":"Cell Growth Differ."},{"key":"2023072513224402200_BIB28","doi-asserted-by":"crossref","first-page":"8219","DOI":"10.1073\/pnas.90.17.8219","volume":"90","year":"1993","journal-title":"Proc. Natl. Acad. Sci. USA."},{"key":"2023072513224402200_BIB29","doi-asserted-by":"crossref","first-page":"394","DOI":"10.1038\/nrc1363","volume":"4","year":"2004","journal-title":"Nat. Rev. Cancer."},{"key":"2023072513224402200_BIB30","doi-asserted-by":"crossref","first-page":"193","DOI":"10.1038\/modpathol.3880035","volume":"13","year":"2000","journal-title":"Mod Pathol."},{"key":"2023072513224402200_BIB31","doi-asserted-by":"crossref","first-page":"489","DOI":"10.1182\/blood.V90.2.489","volume":"90","year":"1997","journal-title":"Blood."},{"key":"2023072513224402200_BIB32","doi-asserted-by":"crossref","first-page":"193","DOI":"10.1038\/35004599","volume":"404","year":"2000","journal-title":"Nature."},{"key":"2023072513224402200_BIB33","doi-asserted-by":"crossref","first-page":"661","DOI":"10.1016\/S0092-8674(00)80453-5","volume":"91","year":"1997","journal-title":"Cell."},{"key":"2023072513224402200_BIB34","doi-asserted-by":"crossref","first-page":"251","DOI":"10.1038\/344251a0","volume":"344","year":"1990","journal-title":"Nature."},{"key":"2023072513224402200_BIB35","doi-asserted-by":"crossref","first-page":"376","DOI":"10.1182\/blood.V89.2.376","volume":"89","year":"1997","journal-title":"Blood."},{"key":"2023072513224402200_BIB36","doi-asserted-by":"crossref","first-page":"5302","DOI":"10.1073\/pnas.94.10.5302","volume":"94","year":"1997","journal-title":"Proc. Natl. Acad. Sci. USA."},{"key":"2023072513224402200_BIB37","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1016\/S1074-7613(00)80587-7","volume":"9","year":"1998","journal-title":"Immunity."},{"key":"2023072513224402200_BIB38","doi-asserted-by":"crossref","first-page":"63","DOI":"10.1016\/S1535-6108(02)00016-8","volume":"1","year":"2002","journal-title":"Cancer Cell."},{"key":"2023072513224402200_BIB39","doi-asserted-by":"crossref","first-page":"10398","DOI":"10.1073\/pnas.171321298","volume":"98","year":"2001","journal-title":"Proc. Natl. Acad. Sci. USA."},{"key":"2023072513224402200_BIB40","doi-asserted-by":"crossref","first-page":"2413","DOI":"10.1101\/gad.12.15.2413","volume":"12","year":"1998","journal-title":"Genes Dev."},{"key":"2023072513224402200_BIB41","doi-asserted-by":"crossref","first-page":"4301","DOI":"10.1128\/MCB.18.7.4301","volume":"18","year":"1998","journal-title":"Mol. Cell. Biol."},{"key":"2023072513224402200_BIB42","doi-asserted-by":"crossref","first-page":"853","DOI":"10.1016\/j.immuni.2004.11.006","volume":"21","year":"2004","journal-title":"Immunity."},{"key":"2023072513224402200_BIB43","first-page":"1639","volume":"104","year":"2004","journal-title":"Blood."},{"key":"2023072513224402200_BIB44","doi-asserted-by":"crossref","first-page":"1267","DOI":"10.1182\/blood-2003-02-0477","volume":"102","year":"2003","journal-title":"Blood."},{"key":"2023072513224402200_BIB45","doi-asserted-by":"crossref","first-page":"726","DOI":"10.1182\/blood.V95.2.726","volume":"95","year":"2000","journal-title":"Blood."},{"key":"2023072513224402200_BIB46","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1309\/6U82-2WNG-4KX3-HBMA","volume":"118","year":"2002","journal-title":"Am. J. Clin. Pathol."},{"key":"2023072513224402200_BIB47","doi-asserted-by":"crossref","first-page":"730","DOI":"10.1038\/nm0797-730","volume":"3","year":"1997","journal-title":"Nat. Med."},{"key":"2023072513224402200_BIB48","doi-asserted-by":"crossref","first-page":"645","DOI":"10.1038\/367645a0","volume":"367","year":"1994","journal-title":"Nature."},{"key":"2023072513224402200_BIB49","doi-asserted-by":"crossref","first-page":"1166","DOI":"10.1182\/blood.V98.4.1166","volume":"98","year":"2001","journal-title":"Blood."},{"key":"2023072513224402200_BIB50","doi-asserted-by":"crossref","first-page":"1029","DOI":"10.1038\/ni973","volume":"4","year":"2003","journal-title":"Nat. Immunol."},{"key":"2023072513224402200_BIB51","doi-asserted-by":"crossref","first-page":"483","DOI":"10.1182\/blood.V100.2.483","volume":"100","year":"2002","journal-title":"Blood."},{"key":"2023072513224402200_BIB52","doi-asserted-by":"crossref","first-page":"4760","DOI":"10.1038\/sj.onc.1206664","volume":"22","year":"2003","journal-title":"Oncogene."},{"key":"2023072513224402200_BIB53","doi-asserted-by":"crossref","first-page":"941","DOI":"10.1084\/jem.194.7.941","volume":"194","year":"2001","journal-title":"J. Exp. Med."},{"key":"2023072513224402200_BIB54","doi-asserted-by":"crossref","first-page":"1002","DOI":"10.1038\/nature02994","volume":"431","year":"2004","journal-title":"Nature."},{"key":"2023072513224402200_BIB55","doi-asserted-by":"crossref","first-page":"659","DOI":"10.1016\/S1074-7613(01)00220-5","volume":"15","year":"2001","journal-title":"Immunity."}],"container-title":["The Journal of Experimental Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/rupress.org\/jem\/article-pdf\/202\/1\/85\/1719255\/jem202185.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/rupress.org\/jem\/article-pdf\/202\/1\/85\/1719255\/jem202185.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,7,25]],"date-time":"2023-07-25T09:25:07Z","timestamp":1690277107000},"score":1,"resource":{"primary":{"URL":"https:\/\/rupress.org\/jem\/article\/202\/1\/85\/52761\/Loss-of-C-EBP-cell-cycle-control-increases-myeloid"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2005,6,27]]},"references-count":55,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2005,7,4]]}},"URL":"https:\/\/doi.org\/10.1084\/jem.20050067","relation":{},"ISSN":["1540-9538","0022-1007"],"issn-type":[{"value":"1540-9538","type":"electronic"},{"value":"0022-1007","type":"print"}],"subject":[],"published":{"date-parts":[[2005,6,27]]}}}