Inactivation of PU.1 in Adult Mice Leads to the Development of Myeloid Leukemia
Genetically primed adult C57BL mice were deleted of exon 5 of the gene encoding the transcription factor PU.1 by IFN activation of Cre recombinase. After a 13-week delay, conditionally deleted ($PU.1^{-/-}$) mice began dying of myeloid leukemia, and 95% of the mice surviving from early postinduction...
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| Veröffentlicht in: | Proceedings of the National Academy of Sciences - PNAS 2006-01, Vol.103 (5), p.1486-1491 |
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| creator | Metcalf, Donald Dakic, Aleksandar Mifsud, Sandra Di Rago, Ladina Wu, Li Nutt, Stephen |
| description | Genetically primed adult C57BL mice were deleted of exon 5 of the gene encoding the transcription factor PU.1 by IFN activation of Cre recombinase. After a 13-week delay, conditionally deleted ($PU.1^{-/-}$) mice began dying of myeloid leukemia, and 95% of the mice surviving from early postinduction death developed transplantable myeloid leukemia whose cells were deleted of PU.1 and uniformly Gr-1 positive. The leukemic cells formed autonomous colonies in semisolid culture with varying clonal efficiency, but colony formation was enhanced by IL-3 and sometimes by granulocyte-macrophage colony-stimulating factor. Nine of 13 tumors analyzed had developed a capacity for autocrine IL-3 or granulocyte-macrophage colony-stimulating factor production, and there was evidence of rearrangement of the IL-3 gene. Acquisition of autocrine growth-factor production and autonomous growth appeared to be major events in the transformation of conditionally deleted$PU.1^{-/-}$cells to fully developed myeloid leukemic populations. |
| doi_str_mv | 10.1073/pnas.0510616103 |
| format | Article |
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After a 13-week delay, conditionally deleted ($PU.1^{-/-}$) mice began dying of myeloid leukemia, and 95% of the mice surviving from early postinduction death developed transplantable myeloid leukemia whose cells were deleted of PU.1 and uniformly Gr-1 positive. The leukemic cells formed autonomous colonies in semisolid culture with varying clonal efficiency, but colony formation was enhanced by IL-3 and sometimes by granulocyte-macrophage colony-stimulating factor. Nine of 13 tumors analyzed had developed a capacity for autocrine IL-3 or granulocyte-macrophage colony-stimulating factor production, and there was evidence of rearrangement of the IL-3 gene. Acquisition of autocrine growth-factor production and autonomous growth appeared to be major events in the transformation of conditionally deleted$PU.1^{-/-}$cells to fully developed myeloid leukemic populations.</description><identifier>ISSN: 0027-8424</identifier><identifier>EISSN: 1091-6490</identifier><identifier>DOI: 10.1073/pnas.0510616103</identifier><identifier>PMID: 16432184</identifier><language>eng</language><publisher>United States: National Academy of Sciences</publisher><subject>Animals ; Biological Sciences ; Bone marrow ; Bone marrow cells ; Bone Marrow Cells - metabolism ; Cell adhesion & migration ; Cell culture ; Cell growth ; Cell Line, Tumor ; Cell Transplantation ; Cultured cells ; Flow Cytometry ; Gene Deletion ; Genes ; Granulocyte-Macrophage Colony-Stimulating Factor - metabolism ; Growth Substances - metabolism ; Interleukin-3 - metabolism ; Leukemia ; Leukemia - metabolism ; Leukemia, Myeloid - genetics ; Leukemia, Myeloid - metabolism ; Medical research ; Mice ; Mice, Inbred C57BL ; Mice, Transgenic ; Myeloid cells ; Myeloid leukemia ; Neoplasm Transplantation ; Proto-Oncogene Proteins - genetics ; Proto-Oncogene Proteins - physiology ; Rodents ; Spleen ; Spleen - metabolism ; Spleen cells ; Time Factors ; Trans-Activators - genetics ; Trans-Activators - physiology ; Tumors</subject><ispartof>Proceedings of the National Academy of Sciences - PNAS, 2006-01, Vol.103 (5), p.1486-1491</ispartof><rights>Copyright 2006 National Academy of Sciences of the United States of America</rights><rights>Copyright National Academy of Sciences Jan 31, 2006</rights><rights>Copyright © 2006, The National Academy of Sciences 2006</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c592t-5fb4cc2796da132be326a342c6364145e7695f8ae6f02d2067a3c1a0edd7e0963</citedby><cites>FETCH-LOGICAL-c592t-5fb4cc2796da132be326a342c6364145e7695f8ae6f02d2067a3c1a0edd7e0963</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Uhttp://www.pnas.org/content/103/5.cover.gif</thumbnail><linktopdf>$$Uhttps://www.jstor.org/stable/pdf/30048399$$EPDF$$P50$$Gjstor$$H</linktopdf><linktohtml>$$Uhttps://www.jstor.org/stable/30048399$$EHTML$$P50$$Gjstor$$H</linktohtml><link.rule.ids>230,314,723,776,780,799,881,27901,27902,53766,53768,57992,58225</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/16432184$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Metcalf, Donald</creatorcontrib><creatorcontrib>Dakic, Aleksandar</creatorcontrib><creatorcontrib>Mifsud, Sandra</creatorcontrib><creatorcontrib>Di Rago, Ladina</creatorcontrib><creatorcontrib>Wu, Li</creatorcontrib><creatorcontrib>Nutt, Stephen</creatorcontrib><title>Inactivation of PU.1 in Adult Mice Leads to the Development of Myeloid Leukemia</title><title>Proceedings of the National Academy of Sciences - PNAS</title><addtitle>Proc Natl Acad Sci U S A</addtitle><description>Genetically primed adult C57BL mice were deleted of exon 5 of the gene encoding the transcription factor PU.1 by IFN activation of Cre recombinase. After a 13-week delay, conditionally deleted ($PU.1^{-/-}$) mice began dying of myeloid leukemia, and 95% of the mice surviving from early postinduction death developed transplantable myeloid leukemia whose cells were deleted of PU.1 and uniformly Gr-1 positive. The leukemic cells formed autonomous colonies in semisolid culture with varying clonal efficiency, but colony formation was enhanced by IL-3 and sometimes by granulocyte-macrophage colony-stimulating factor. Nine of 13 tumors analyzed had developed a capacity for autocrine IL-3 or granulocyte-macrophage colony-stimulating factor production, and there was evidence of rearrangement of the IL-3 gene. Acquisition of autocrine growth-factor production and autonomous growth appeared to be major events in the transformation of conditionally deleted$PU.1^{-/-}$cells to fully developed myeloid leukemic populations.</description><subject>Animals</subject><subject>Biological Sciences</subject><subject>Bone marrow</subject><subject>Bone marrow cells</subject><subject>Bone Marrow Cells - metabolism</subject><subject>Cell adhesion & migration</subject><subject>Cell culture</subject><subject>Cell growth</subject><subject>Cell Line, Tumor</subject><subject>Cell Transplantation</subject><subject>Cultured cells</subject><subject>Flow Cytometry</subject><subject>Gene Deletion</subject><subject>Genes</subject><subject>Granulocyte-Macrophage Colony-Stimulating Factor - metabolism</subject><subject>Growth Substances - metabolism</subject><subject>Interleukin-3 - metabolism</subject><subject>Leukemia</subject><subject>Leukemia - metabolism</subject><subject>Leukemia, Myeloid - genetics</subject><subject>Leukemia, Myeloid - metabolism</subject><subject>Medical research</subject><subject>Mice</subject><subject>Mice, Inbred C57BL</subject><subject>Mice, Transgenic</subject><subject>Myeloid cells</subject><subject>Myeloid leukemia</subject><subject>Neoplasm Transplantation</subject><subject>Proto-Oncogene Proteins - genetics</subject><subject>Proto-Oncogene Proteins - physiology</subject><subject>Rodents</subject><subject>Spleen</subject><subject>Spleen - metabolism</subject><subject>Spleen cells</subject><subject>Time Factors</subject><subject>Trans-Activators - genetics</subject><subject>Trans-Activators - physiology</subject><subject>Tumors</subject><issn>0027-8424</issn><issn>1091-6490</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2006</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kU1v1DAQhi1ERbeFMydQxKGcsh1_xxekqny00lblQM-W13GolyTexs6K_nscdtVtK8TJsvzM45l5EXqLYY5B0tN1b-IcOAaBBQb6As0wKFwKpuAlmgEQWVaMsEN0FOMKABSv4BU6xIJRgis2Q9eXvbHJb0zyoS9CU3y_mePC98VZPbapuPLWFQtn6likUKRbV3x2G9eGdef6NOFX9_nm68yMv1znzWt00Jg2uje78xjdfP3y4_yiXFx_uzw_W5SWK5JK3iyZtUQqURtMydJRIgxlxAoqGGbcSaF4UxknGiA1ASENtdiAq2vpQAl6jD5tvetx2bna5nYG0-r14Dsz3OtgvH760vtb_TNsNKYCuGJZcLITDOFudDHpzkfr2tb0LoxRy7xeyv_-9H8QSyZ4JSfjh2fgKoxDn7egCWAiKy6rDJ1uITuEGAfXPLSMQU-R6ilSvY80V7x_POme32WYgY87YKrc66jmGrNK6GZs2-R-p0eqf5MZeLcFVjGF4YGgAKyiStE_x728tw</recordid><startdate>20060131</startdate><enddate>20060131</enddate><creator>Metcalf, Donald</creator><creator>Dakic, Aleksandar</creator><creator>Mifsud, Sandra</creator><creator>Di Rago, Ladina</creator><creator>Wu, Li</creator><creator>Nutt, Stephen</creator><general>National Academy of Sciences</general><general>National Acad Sciences</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7QG</scope><scope>7QL</scope><scope>7QP</scope><scope>7QR</scope><scope>7SN</scope><scope>7SS</scope><scope>7T5</scope><scope>7TK</scope><scope>7TM</scope><scope>7TO</scope><scope>7U9</scope><scope>8FD</scope><scope>C1K</scope><scope>FR3</scope><scope>H94</scope><scope>M7N</scope><scope>P64</scope><scope>RC3</scope><scope>7X8</scope><scope>5PM</scope></search><sort><creationdate>20060131</creationdate><title>Inactivation of PU.1 in Adult Mice Leads to the Development of Myeloid Leukemia</title><author>Metcalf, Donald ; 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After a 13-week delay, conditionally deleted ($PU.1^{-/-}$) mice began dying of myeloid leukemia, and 95% of the mice surviving from early postinduction death developed transplantable myeloid leukemia whose cells were deleted of PU.1 and uniformly Gr-1 positive. The leukemic cells formed autonomous colonies in semisolid culture with varying clonal efficiency, but colony formation was enhanced by IL-3 and sometimes by granulocyte-macrophage colony-stimulating factor. Nine of 13 tumors analyzed had developed a capacity for autocrine IL-3 or granulocyte-macrophage colony-stimulating factor production, and there was evidence of rearrangement of the IL-3 gene. Acquisition of autocrine growth-factor production and autonomous growth appeared to be major events in the transformation of conditionally deleted$PU.1^{-/-}$cells to fully developed myeloid leukemic populations.</abstract><cop>United States</cop><pub>National Academy of Sciences</pub><pmid>16432184</pmid><doi>10.1073/pnas.0510616103</doi><tpages>6</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | Animals Biological Sciences Bone marrow Bone marrow cells Bone Marrow Cells - metabolism Cell adhesion & migration Cell culture Cell growth Cell Line, Tumor Cell Transplantation Cultured cells Flow Cytometry Gene Deletion Genes Granulocyte-Macrophage Colony-Stimulating Factor - metabolism Growth Substances - metabolism Interleukin-3 - metabolism Leukemia Leukemia - metabolism Leukemia, Myeloid - genetics Leukemia, Myeloid - metabolism Medical research Mice Mice, Inbred C57BL Mice, Transgenic Myeloid cells Myeloid leukemia Neoplasm Transplantation Proto-Oncogene Proteins - genetics Proto-Oncogene Proteins - physiology Rodents Spleen Spleen - metabolism Spleen cells Time Factors Trans-Activators - genetics Trans-Activators - physiology Tumors |
| title | Inactivation of PU.1 in Adult Mice Leads to the Development of Myeloid Leukemia |
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