{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,8]],"date-time":"2026-01-08T01:48:13Z","timestamp":1767836893382,"version":"3.49.0"},"reference-count":46,"publisher":"Proceedings of the National Academy of Sciences","issue":"18","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2001,8,28]]},"abstract":"<jats:p>\n            The t(8;21) is one of the most frequent chromosomal abnormalities associated with acute myeloid leukemia (AML). The translocation, which involves the\n            <jats:italic>AML1<\/jats:italic>\n            gene on chromosome 21 and the\n            <jats:italic>ETO<\/jats:italic>\n            gene on chromosome 8, generates an AML1-ETO fusion transcription factor. To examine the effect of the AML1-ETO fusion protein on leukemogenesis, we made transgenic mice in which expression of AML1-ETO is under the control of the human\n            <jats:italic>MRP8<\/jats:italic>\n            promoter (hMRP8-AML1-ETO). AML1-ETO is specifically expressed in myeloid cells, including common myeloid progenitors of hMRP8-AML1-ETO transgenic mice. The transgenic mice were healthy during their life spans, suggesting that AML1-ETO alone is not sufficient for leukemogenesis. However, after treatment of newborn hMRP8-AML1-ETO transgenic mice and their wild-type littermates with a strong DNA-alkylating mutagen,\n            <jats:italic>N-<\/jats:italic>\n            ethyl-\n            <jats:italic>N<\/jats:italic>\n            -nitrosourea, 55% of transgenic mice developed AML and the other 45% of transgenic mice and all of the wild-type littermates developed acute T lymphoblastic leukemia. Our results provide direct evidence that AML1-ETO is critical for causing myeloid leukemia, but one or more additional mutations are required for leukemogenesis. The hMRP8-AML1-ETO-transgenic mice provide an excellent model that can be used to isolate additional genetic events and to further understand the molecular pathogenesis of AML1-ETO-related leukemia.\n          <\/jats:p>","DOI":"10.1073\/pnas.171321298","type":"journal-article","created":{"date-parts":[[2002,7,26]],"date-time":"2002-07-26T14:45:09Z","timestamp":1027694709000},"page":"10398-10403","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":354,"title":["AML1-ETO expression is directly involved in the development of acute myeloid leukemia in the presence of additional mutations"],"prefix":"10.1073","volume":"98","author":[{"given":"Youzhong","family":"Yuan","sequence":"first","affiliation":[{"name":"Department of Molecular and Experimental Medicine, The Scripps Research Institute, La Jolla, CA 92037; Department of Pathology and Development Biology, Stanford University School of Medicine, Stanford, CA 94305; Department of Medicine, Harvard Medical School, Boston, MA 02115; and Department of Cancer Immunology and AIDS, Dana\u2013Farber Cancer Institute, Boston, MA 02115"}]},{"given":"Liming","family":"Zhou","sequence":"additional","affiliation":[{"name":"Department of Molecular and Experimental Medicine, The Scripps Research Institute, La Jolla, CA 92037; Department of Pathology and Development Biology, Stanford University School of Medicine, Stanford, CA 94305; Department of Medicine, Harvard Medical School, Boston, MA 02115; and Department of Cancer Immunology and AIDS, Dana\u2013Farber Cancer Institute, Boston, MA 02115"}]},{"given":"Toshihiro","family":"Miyamoto","sequence":"additional","affiliation":[{"name":"Department of Molecular and Experimental Medicine, The Scripps Research Institute, La Jolla, CA 92037; Department of Pathology and Development Biology, Stanford University School of Medicine, Stanford, CA 94305; Department of Medicine, Harvard Medical School, Boston, MA 02115; and Department of Cancer Immunology and AIDS, Dana\u2013Farber Cancer Institute, Boston, MA 02115"}]},{"given":"Hiromi","family":"Iwasaki","sequence":"additional","affiliation":[{"name":"Department of Molecular and Experimental Medicine, The Scripps Research Institute, La Jolla, CA 92037; Department of Pathology and Development Biology, Stanford University School of Medicine, Stanford, CA 94305; Department of Medicine, Harvard Medical School, Boston, MA 02115; and Department of Cancer Immunology and AIDS, Dana\u2013Farber Cancer Institute, Boston, MA 02115"}]},{"given":"Nari","family":"Harakawa","sequence":"additional","affiliation":[{"name":"Department of Molecular and Experimental Medicine, The Scripps Research Institute, La Jolla, CA 92037; Department of Pathology and Development Biology, Stanford University School of Medicine, Stanford, CA 94305; Department of Medicine, Harvard Medical School, Boston, MA 02115; and Department of Cancer Immunology and AIDS, Dana\u2013Farber Cancer Institute, Boston, MA 02115"}]},{"given":"Christopher J.","family":"Hetherington","sequence":"additional","affiliation":[{"name":"Department of Molecular and Experimental Medicine, The Scripps Research Institute, La Jolla, CA 92037; Department of Pathology and Development Biology, Stanford University School of Medicine, Stanford, CA 94305; Department of Medicine, Harvard Medical School, Boston, MA 02115; and Department of Cancer Immunology and AIDS, Dana\u2013Farber Cancer Institute, Boston, MA 02115"}]},{"given":"Sebastien A.","family":"Burel","sequence":"additional","affiliation":[{"name":"Department of Molecular and Experimental Medicine, The Scripps Research Institute, La Jolla, CA 92037; Department of Pathology and Development Biology, Stanford University School of Medicine, Stanford, CA 94305; Department of Medicine, Harvard Medical School, Boston, MA 02115; and Department of Cancer Immunology and AIDS, Dana\u2013Farber Cancer Institute, Boston, MA 02115"}]},{"given":"Eric","family":"Lagasse","sequence":"additional","affiliation":[{"name":"Department of Molecular and Experimental Medicine, The Scripps Research Institute, La Jolla, CA 92037; Department of Pathology and Development Biology, Stanford University School of Medicine, Stanford, CA 94305; Department of Medicine, Harvard Medical School, Boston, MA 02115; and Department of Cancer Immunology and AIDS, Dana\u2013Farber Cancer Institute, Boston, MA 02115"}]},{"given":"Irving L.","family":"Weissman","sequence":"additional","affiliation":[{"name":"Department of Molecular and Experimental Medicine, The Scripps Research Institute, La Jolla, CA 92037; Department of Pathology and Development Biology, Stanford University School of Medicine, Stanford, CA 94305; Department of Medicine, Harvard Medical School, Boston, MA 02115; and Department of Cancer Immunology and AIDS, Dana\u2013Farber Cancer Institute, Boston, MA 02115"}]},{"given":"Koichi","family":"Akashi","sequence":"additional","affiliation":[{"name":"Department of Molecular and Experimental Medicine, The Scripps Research Institute, La Jolla, CA 92037; Department of Pathology and Development Biology, Stanford University School of Medicine, Stanford, CA 94305; Department of Medicine, Harvard Medical School, Boston, MA 02115; and Department of Cancer Immunology and AIDS, Dana\u2013Farber Cancer Institute, Boston, MA 02115"}]},{"given":"Dong-Er","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Molecular and Experimental Medicine, The Scripps Research Institute, La Jolla, CA 92037; Department of Pathology and Development Biology, Stanford University School of Medicine, Stanford, CA 94305; Department of Medicine, Harvard Medical School, Boston, MA 02115; and Department of Cancer Immunology and AIDS, Dana\u2013Farber Cancer Institute, Boston, MA 02115"}]}],"member":"341","published-online":{"date-parts":[[2001,8,28]]},"reference":[{"key":"e_1_3_3_1_2","doi-asserted-by":"publisher","DOI":"10.1006\/scdb.2000.0183"},{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1038\/sj.leu.2401590"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0378-1119(00)00014-7"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.88.23.10431"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.15.4.1974"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1016\/0168-9525(93)90026-E"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1128\/mcb.13.6.3324-3339.1993"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1002\/j.1460-2075.1994.tb06288.x"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V81.4.883.883"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.92.11.4917"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V91.11.4028"},{"key":"e_1_3_3_12_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V95.12.4011"},{"key":"e_1_3_3_13_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.8351518"},{"key":"e_1_3_3_14_2","doi-asserted-by":"publisher","DOI":"10.1038\/ng0397-303"},{"key":"e_1_3_3_15_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V91.9.3134"},{"key":"e_1_3_3_16_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(00)80986-1"},{"key":"e_1_3_3_17_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.93.8.3444"},{"key":"e_1_3_3_18_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V96.6.2108.h8002108_2108_2115"},{"key":"e_1_3_3_19_2","doi-asserted-by":"publisher","DOI":"10.1093\/embo-reports\/kvd027"},{"key":"e_1_3_3_20_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V79.8.1907.1907"},{"key":"e_1_3_3_21_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.94.6.2551"},{"key":"e_1_3_3_22_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.95.20.11863"},{"key":"e_1_3_3_23_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.179.3.1047"},{"key":"e_1_3_3_24_2","doi-asserted-by":"publisher","DOI":"10.1038\/35004599"},{"key":"e_1_3_3_25_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(00)80453-5"},{"key":"e_1_3_3_26_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.97.13.7521"},{"key":"e_1_3_3_27_2","doi-asserted-by":"publisher","DOI":"10.1038\/340061a0"},{"key":"e_1_3_3_28_2","doi-asserted-by":"publisher","DOI":"10.1038\/13776"},{"key":"e_1_3_3_29_2","first-page":"845","volume":"64","author":"Frei J V","year":"1980","unstructured":"J V Frei, P D Lawley J Natl Cancer Inst 64, 845\u2013856 (1980).","journal-title":"J Natl Cancer Inst"},{"key":"e_1_3_3_30_2","first-page":"958","volume":"51","author":"Breuer M","year":"1991","unstructured":"M Breuer, E Wientjens, S Verbeek, R Slebos, A Berns Cancer Res 51, 958\u2013963 (1991).","journal-title":"Cancer Res"},{"key":"e_1_3_3_31_2","doi-asserted-by":"publisher","DOI":"10.1038\/344251a0"},{"key":"e_1_3_3_32_2","doi-asserted-by":"publisher","DOI":"10.1038\/71691"},{"key":"e_1_3_3_33_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.94.10.5302"},{"key":"e_1_3_3_34_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V89.2.376"},{"key":"e_1_3_3_35_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.93.15.7900"},{"key":"e_1_3_3_36_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.96.11.6318"},{"key":"e_1_3_3_37_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1097-2765(00)00111-8"},{"key":"e_1_3_3_38_2","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.19.6.4443"},{"key":"e_1_3_3_39_2","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.21.16.5577-5590.2001"},{"key":"e_1_3_3_40_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.030421197"},{"key":"e_1_3_3_41_2","doi-asserted-by":"publisher","DOI":"10.1128\/mcb.8.1.301-308.1988"},{"key":"e_1_3_3_42_2","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/8.10.1955"},{"key":"e_1_3_3_43_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.82.19.6619"},{"key":"e_1_3_3_44_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V96.1.288"},{"key":"e_1_3_3_45_2","doi-asserted-by":"publisher","DOI":"10.1006\/bcmd.2001.0391"},{"key":"e_1_3_3_46_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V95.2.726"}],"container-title":["Proceedings of the National Academy of Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/pnas.org\/doi\/pdf\/10.1073\/pnas.171321298","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,4,13]],"date-time":"2022-04-13T06:46:49Z","timestamp":1649832409000},"score":1,"resource":{"primary":{"URL":"https:\/\/pnas.org\/doi\/full\/10.1073\/pnas.171321298"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2001,8,28]]},"references-count":46,"journal-issue":{"issue":"18","published-print":{"date-parts":[[2001,8,28]]}},"alternative-id":["10.1073\/pnas.171321298"],"URL":"https:\/\/doi.org\/10.1073\/pnas.171321298","relation":{},"ISSN":["0027-8424","1091-6490"],"issn-type":[{"value":"0027-8424","type":"print"},{"value":"1091-6490","type":"electronic"}],"subject":[],"published":{"date-parts":[[2001,8,28]]},"assertion":[{"value":"2001-06-25","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2001-08-28","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}