Dysplastic definitive hematopoiesis in AML1/EVI1 knock-in embryos
The AML1/EVI1 chimeric gene is created by the t(3;21)(q26;q22) chromosomal translocation seen in patients with leukemic transformation of myelodysplastic syndrome or blastic crisis of chronic myelogenous leukemia. We knocked-in the AML1/EVI1 chimeric gene into mouse Aml1 genomic locus to explore its...
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Veröffentlicht in: | Blood 2005-09, Vol.106 (6), p.2147-2155 |
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creator | Maki, Kazuhiro Yamagata, Tetsuya Asai, Takashi Yamazaki, Ieharu Oda, Hideaki Hirai, Hisamaru Mitani, Kinuko |
description | The AML1/EVI1 chimeric gene is created by the t(3;21)(q26;q22) chromosomal translocation seen in patients with leukemic transformation of myelodysplastic syndrome or blastic crisis of chronic myelogenous leukemia. We knocked-in the AML1/EVI1 chimeric gene into mouse Aml1 genomic locus to explore its effect in developmental hematopoiesis in vivo. AML1/EVI1/+ embryo showed defective hematopoiesis in the fetal liver and died around embryonic day 13.5 (E13.5) as a result of hemorrhage in the central nervous system. The peripheral blood had yolk-sac-derived nucleated erythroblasts but lacked erythrocytes of the definitive origin. Although E12.5 fetal liver contained progenitors for macrophage only, E13.5 fetal liver contained multilineage progenitors capable of differentiating into dysplastic myelocyte and megakaryocyte. No erythroid progenitor was detected in E12.5 or E13.5 fetal liver. Hematopoietic progenitors from E13.5 AML1/EVI1/+ fetal liver were highly capable of self-renewal compared with those from wild-type liver. Maintained expression of PU.1 gene and decreased expression of LMO2 and SCL genes may explain the aberrant hematopoiesis in AML1/EVI1/+ fetal liver. (Blood. 2005;106:2147-2155) |
doi_str_mv | 10.1182/blood-2004-11-4330 |
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We knocked-in the AML1/EVI1 chimeric gene into mouse Aml1 genomic locus to explore its effect in developmental hematopoiesis in vivo. AML1/EVI1/+ embryo showed defective hematopoiesis in the fetal liver and died around embryonic day 13.5 (E13.5) as a result of hemorrhage in the central nervous system. The peripheral blood had yolk-sac-derived nucleated erythroblasts but lacked erythrocytes of the definitive origin. Although E12.5 fetal liver contained progenitors for macrophage only, E13.5 fetal liver contained multilineage progenitors capable of differentiating into dysplastic myelocyte and megakaryocyte. No erythroid progenitor was detected in E12.5 or E13.5 fetal liver. Hematopoietic progenitors from E13.5 AML1/EVI1/+ fetal liver were highly capable of self-renewal compared with those from wild-type liver. Maintained expression of PU.1 gene and decreased expression of LMO2 and SCL genes may explain the aberrant hematopoiesis in AML1/EVI1/+ fetal liver. (Blood. 2005;106:2147-2155)</description><identifier>ISSN: 0006-4971</identifier><identifier>EISSN: 1528-0020</identifier><identifier>DOI: 10.1182/blood-2004-11-4330</identifier><identifier>PMID: 15914564</identifier><language>eng</language><publisher>Washington, DC: Elsevier Inc</publisher><subject>Adaptor Proteins, Signal Transducing ; Animals ; Biological and medical sciences ; Core Binding Factor Alpha 2 Subunit ; DNA-Binding Proteins - genetics ; Embryo, Mammalian ; Erythroblasts ; Hematologic and hematopoietic diseases ; Hematopoiesis - genetics ; Hematopoietic Stem Cells - cytology ; Intracranial Hemorrhages - etiology ; Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis ; LIM Domain Proteins ; Liver - cytology ; Liver - embryology ; MDS1 and EVI1 Complex Locus Protein ; Medical sciences ; Metalloproteins - genetics ; Mice ; Mice, Transgenic ; Multipotent Stem Cells ; Oncogene Proteins, Fusion - genetics ; Oncogene Proteins, Fusion - physiology ; Proto-Oncogene Proteins - genetics ; Proto-Oncogenes - genetics ; Trans-Activators - genetics ; Transcription Factors - genetics</subject><ispartof>Blood, 2005-09, Vol.106 (6), p.2147-2155</ispartof><rights>2005 American Society of Hematology</rights><rights>2006 INIST-CNRS</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c4090-9f0c4ea58cd68233201cec4c3968b6184e011cf5b47e2a477345ca0cfa2ea9803</citedby><cites>FETCH-LOGICAL-c4090-9f0c4ea58cd68233201cec4c3968b6184e011cf5b47e2a477345ca0cfa2ea9803</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,27923,27924</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=17147368$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/15914564$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Maki, Kazuhiro</creatorcontrib><creatorcontrib>Yamagata, Tetsuya</creatorcontrib><creatorcontrib>Asai, Takashi</creatorcontrib><creatorcontrib>Yamazaki, Ieharu</creatorcontrib><creatorcontrib>Oda, Hideaki</creatorcontrib><creatorcontrib>Hirai, Hisamaru</creatorcontrib><creatorcontrib>Mitani, Kinuko</creatorcontrib><title>Dysplastic definitive hematopoiesis in AML1/EVI1 knock-in embryos</title><title>Blood</title><addtitle>Blood</addtitle><description>The AML1/EVI1 chimeric gene is created by the t(3;21)(q26;q22) chromosomal translocation seen in patients with leukemic transformation of myelodysplastic syndrome or blastic crisis of chronic myelogenous leukemia. We knocked-in the AML1/EVI1 chimeric gene into mouse Aml1 genomic locus to explore its effect in developmental hematopoiesis in vivo. AML1/EVI1/+ embryo showed defective hematopoiesis in the fetal liver and died around embryonic day 13.5 (E13.5) as a result of hemorrhage in the central nervous system. The peripheral blood had yolk-sac-derived nucleated erythroblasts but lacked erythrocytes of the definitive origin. Although E12.5 fetal liver contained progenitors for macrophage only, E13.5 fetal liver contained multilineage progenitors capable of differentiating into dysplastic myelocyte and megakaryocyte. No erythroid progenitor was detected in E12.5 or E13.5 fetal liver. Hematopoietic progenitors from E13.5 AML1/EVI1/+ fetal liver were highly capable of self-renewal compared with those from wild-type liver. Maintained expression of PU.1 gene and decreased expression of LMO2 and SCL genes may explain the aberrant hematopoiesis in AML1/EVI1/+ fetal liver. (Blood. 2005;106:2147-2155)</description><subject>Adaptor Proteins, Signal Transducing</subject><subject>Animals</subject><subject>Biological and medical sciences</subject><subject>Core Binding Factor Alpha 2 Subunit</subject><subject>DNA-Binding Proteins - genetics</subject><subject>Embryo, Mammalian</subject><subject>Erythroblasts</subject><subject>Hematologic and hematopoietic diseases</subject><subject>Hematopoiesis - genetics</subject><subject>Hematopoietic Stem Cells - cytology</subject><subject>Intracranial Hemorrhages - etiology</subject><subject>Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis</subject><subject>LIM Domain Proteins</subject><subject>Liver - cytology</subject><subject>Liver - embryology</subject><subject>MDS1 and EVI1 Complex Locus Protein</subject><subject>Medical sciences</subject><subject>Metalloproteins - genetics</subject><subject>Mice</subject><subject>Mice, Transgenic</subject><subject>Multipotent Stem Cells</subject><subject>Oncogene Proteins, Fusion - genetics</subject><subject>Oncogene Proteins, Fusion - physiology</subject><subject>Proto-Oncogene Proteins - genetics</subject><subject>Proto-Oncogenes - genetics</subject><subject>Trans-Activators - genetics</subject><subject>Transcription Factors - genetics</subject><issn>0006-4971</issn><issn>1528-0020</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2005</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kE1v1DAQhi0EotvSP8AB5QI30xl_JI7EZVVaqLSIC_RqOZOJME3iJc5W2n_fbHel3jiNZvS8r0aPEO8RPiM6ddX0KbVSARiJKI3W8Eqs0ConARS8FisAKKWpKzwT5zn_BUCjlX0rztDWaGxpVmL9dZ-3fchzpKLlLo5xjo9c_OEhzGmbIueYizgW6x8bvLq5v8PiYUz0IJcTD820T_mdeNOFPvPlaV6I37c3v66_y83Pb3fX640kAzXIugMyHKyjtnRKawVITIZ0XbqmRGcYEKmzjalYBVNV2lgKQF1QHGoH-kJ8OvZup_Rvx3n2Q8zEfR9GTrvsS2ctutosoDqCNKWcJ-78dopDmPYewR_E-Wdx_iBu2f1B3BL6cGrfNQO3L5GTqQX4eAJCptB3Uxgp5heuQlPp0i3clyPHi4vHyJPPFHkkbuPENPs2xf_98QT-Bon9</recordid><startdate>20050915</startdate><enddate>20050915</enddate><creator>Maki, Kazuhiro</creator><creator>Yamagata, Tetsuya</creator><creator>Asai, Takashi</creator><creator>Yamazaki, Ieharu</creator><creator>Oda, Hideaki</creator><creator>Hirai, Hisamaru</creator><creator>Mitani, Kinuko</creator><general>Elsevier Inc</general><general>The Americain Society of Hematology</general><scope>6I.</scope><scope>AAFTH</scope><scope>IQODW</scope><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>7X8</scope></search><sort><creationdate>20050915</creationdate><title>Dysplastic definitive hematopoiesis in AML1/EVI1 knock-in embryos</title><author>Maki, Kazuhiro ; Yamagata, Tetsuya ; Asai, Takashi ; Yamazaki, Ieharu ; Oda, Hideaki ; Hirai, Hisamaru ; Mitani, Kinuko</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c4090-9f0c4ea58cd68233201cec4c3968b6184e011cf5b47e2a477345ca0cfa2ea9803</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2005</creationdate><topic>Adaptor Proteins, Signal Transducing</topic><topic>Animals</topic><topic>Biological and medical sciences</topic><topic>Core Binding Factor Alpha 2 Subunit</topic><topic>DNA-Binding Proteins - genetics</topic><topic>Embryo, Mammalian</topic><topic>Erythroblasts</topic><topic>Hematologic and hematopoietic diseases</topic><topic>Hematopoiesis - genetics</topic><topic>Hematopoietic Stem Cells - cytology</topic><topic>Intracranial Hemorrhages - etiology</topic><topic>Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis</topic><topic>LIM Domain Proteins</topic><topic>Liver - cytology</topic><topic>Liver - embryology</topic><topic>MDS1 and EVI1 Complex Locus Protein</topic><topic>Medical sciences</topic><topic>Metalloproteins - genetics</topic><topic>Mice</topic><topic>Mice, Transgenic</topic><topic>Multipotent Stem Cells</topic><topic>Oncogene Proteins, Fusion - genetics</topic><topic>Oncogene Proteins, Fusion - physiology</topic><topic>Proto-Oncogene Proteins - genetics</topic><topic>Proto-Oncogenes - genetics</topic><topic>Trans-Activators - genetics</topic><topic>Transcription Factors - genetics</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Maki, Kazuhiro</creatorcontrib><creatorcontrib>Yamagata, Tetsuya</creatorcontrib><creatorcontrib>Asai, Takashi</creatorcontrib><creatorcontrib>Yamazaki, Ieharu</creatorcontrib><creatorcontrib>Oda, Hideaki</creatorcontrib><creatorcontrib>Hirai, Hisamaru</creatorcontrib><creatorcontrib>Mitani, Kinuko</creatorcontrib><collection>ScienceDirect Open Access Titles</collection><collection>Elsevier:ScienceDirect:Open Access</collection><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>Blood</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Maki, Kazuhiro</au><au>Yamagata, Tetsuya</au><au>Asai, Takashi</au><au>Yamazaki, Ieharu</au><au>Oda, Hideaki</au><au>Hirai, Hisamaru</au><au>Mitani, Kinuko</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Dysplastic definitive hematopoiesis in AML1/EVI1 knock-in embryos</atitle><jtitle>Blood</jtitle><addtitle>Blood</addtitle><date>2005-09-15</date><risdate>2005</risdate><volume>106</volume><issue>6</issue><spage>2147</spage><epage>2155</epage><pages>2147-2155</pages><issn>0006-4971</issn><eissn>1528-0020</eissn><abstract>The AML1/EVI1 chimeric gene is created by the t(3;21)(q26;q22) chromosomal translocation seen in patients with leukemic transformation of myelodysplastic syndrome or blastic crisis of chronic myelogenous leukemia. We knocked-in the AML1/EVI1 chimeric gene into mouse Aml1 genomic locus to explore its effect in developmental hematopoiesis in vivo. AML1/EVI1/+ embryo showed defective hematopoiesis in the fetal liver and died around embryonic day 13.5 (E13.5) as a result of hemorrhage in the central nervous system. The peripheral blood had yolk-sac-derived nucleated erythroblasts but lacked erythrocytes of the definitive origin. Although E12.5 fetal liver contained progenitors for macrophage only, E13.5 fetal liver contained multilineage progenitors capable of differentiating into dysplastic myelocyte and megakaryocyte. No erythroid progenitor was detected in E12.5 or E13.5 fetal liver. Hematopoietic progenitors from E13.5 AML1/EVI1/+ fetal liver were highly capable of self-renewal compared with those from wild-type liver. Maintained expression of PU.1 gene and decreased expression of LMO2 and SCL genes may explain the aberrant hematopoiesis in AML1/EVI1/+ fetal liver. (Blood. 2005;106:2147-2155)</abstract><cop>Washington, DC</cop><pub>Elsevier Inc</pub><pmid>15914564</pmid><doi>10.1182/blood-2004-11-4330</doi><tpages>9</tpages><oa>free_for_read</oa></addata></record> |
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subjects | Adaptor Proteins, Signal Transducing Animals Biological and medical sciences Core Binding Factor Alpha 2 Subunit DNA-Binding Proteins - genetics Embryo, Mammalian Erythroblasts Hematologic and hematopoietic diseases Hematopoiesis - genetics Hematopoietic Stem Cells - cytology Intracranial Hemorrhages - etiology Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis LIM Domain Proteins Liver - cytology Liver - embryology MDS1 and EVI1 Complex Locus Protein Medical sciences Metalloproteins - genetics Mice Mice, Transgenic Multipotent Stem Cells Oncogene Proteins, Fusion - genetics Oncogene Proteins, Fusion - physiology Proto-Oncogene Proteins - genetics Proto-Oncogenes - genetics Trans-Activators - genetics Transcription Factors - genetics |
title | Dysplastic definitive hematopoiesis in AML1/EVI1 knock-in embryos |
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