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Expression of a Knocked-In AML1-ETO Leukemia Gene Inhibits the Establishment of Normal Definitive Hematopoiesis and Directly Generates Dysplastic Hematopoietic Progenitors
DC Field | Value | Language |
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dc.contributor.author | 유철주 | - |
dc.date.accessioned | 2016-02-19T11:14:15Z | - |
dc.date.available | 2016-02-19T11:14:15Z | - |
dc.date.issued | 1998 | - |
dc.identifier.issn | 0006-4971 | - |
dc.identifier.uri | https://ir.ymlib.yonsei.ac.kr/handle/22282913/142700 | - |
dc.description.abstract | The t(8;21)-encoded AML1-ETO chimeric product is believed to be causally involved in up to 15% of acute myelogenous leukemias through an as yet unknown mechanism. To directly investigate the role of AML1-ETO in leukemogenesis, we used gene targeting to create an AML1-ETO "knock-in" allele that mimics the t(8;21). Unexpectedly, embryos heterozygous for AML1-ETO (AML1-ETO/+) died around E13.5 from a complete absence of normal fetal liver-derived definitive hematopoiesis and lethal hemorrhages. This phenotype was similar to that seen following homozygous disruption of either AML1 or CBFbeta. However, in contrast to AML1- or CBFbeta-deficient embryos, fetal livers from AML1-ETO/+ embryos contained dysplastic multilineage hematopoietic progenitors that had an abnormally high self-renewal capacity in vitro. To further document the role of AML1-ETO in these growth abnormalities, we used retroviral transduction to express AML1-ETO in murine adult bone marrow-derived hematopoietic progenitors. AML1-ETO-expressing cells were again found to have an increased self-renewal capacity and could be readily established into immortalized cell lines in vitro. Taken together, these studies suggest that AML1-ETO not only neutralizes the normal biologic activity of AML1 but also directly induces aberrant hematopoietic cell proliferation. | - |
dc.description.statementOfResponsibility | open | - |
dc.format.extent | 3134~3143 | - |
dc.relation.isPartOf | BLOOD | - |
dc.rights | CC BY-NC-ND 2.0 KR | - |
dc.rights.uri | https://creativecommons.org/licenses/by-nc-nd/2.0/kr/ | - |
dc.title | Expression of a Knocked-In AML1-ETO Leukemia Gene Inhibits the Establishment of Normal Definitive Hematopoiesis and Directly Generates Dysplastic Hematopoietic Progenitors | - |
dc.type | Article | - |
dc.contributor.college | College of Medicine (의과대학) | - |
dc.contributor.department | Dept. of Pediatrics (소아과학) | - |
dc.contributor.googleauthor | Tsukasa Okuda | - |
dc.contributor.googleauthor | Zhongling Cai | - |
dc.contributor.googleauthor | Shouli Yang | - |
dc.contributor.googleauthor | Noel Lenny | - |
dc.contributor.googleauthor | Chuhl-joo Lyu | - |
dc.contributor.googleauthor | Jan M.A. van Deursen | - |
dc.contributor.googleauthor | Hironori Harada | - |
dc.contributor.googleauthor | James R. Downing | - |
dc.admin.author | false | - |
dc.admin.mapping | false | - |
dc.contributor.localId | A02524 | - |
dc.relation.journalcode | J00341 | - |
dc.identifier.eissn | 1528-0020 | - |
dc.contributor.alternativeName | Lyu, Chuhl Joo | - |
dc.contributor.affiliatedAuthor | Lyu, Chuhl Joo | - |
dc.rights.accessRights | free | - |
dc.citation.volume | 91 | - |
dc.citation.number | 9 | - |
dc.citation.startPage | 3134 | - |
dc.citation.endPage | 3143 | - |
dc.identifier.bibliographicCitation | BLOOD, Vol.91(9) : 3134-3143, 1998 | - |
dc.identifier.rimsid | 29777 | - |
dc.type.rims | ART | - |
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