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DC Field | Value | Language |
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dc.citation.endPage | 2659 | - |
dc.citation.number | 12 | - |
dc.citation.startPage | 2641 | - |
dc.citation.title | JOURNAL OF EXPERIMENTAL MEDICINE | - |
dc.citation.volume | 210 | - |
dc.contributor.author | Abdel-Wahab, Omar | - |
dc.contributor.author | Gao, Jie | - |
dc.contributor.author | Adli, Mazhar | - |
dc.contributor.author | Dey, Anwesha | - |
dc.contributor.author | Trimarchi, Thomas | - |
dc.contributor.author | Chung, Young Rock | - |
dc.contributor.author | Kuscu, Cem | - |
dc.contributor.author | Hricik, Todd | - |
dc.contributor.author | Ndiaye-Lobry, Delphine | - |
dc.contributor.author | LaFave, Lindsay M. | - |
dc.contributor.author | Koche, Richard | - |
dc.contributor.author | Shih, Alan H. | - |
dc.contributor.author | Guryanova, Olga A. | - |
dc.contributor.author | Kim, Eunhee | - |
dc.contributor.author | Li, Sheng | - |
dc.contributor.author | Pandey, Suveg | - |
dc.contributor.author | Shin, Joseph Y. | - |
dc.contributor.author | Telis, Leon | - |
dc.contributor.author | Liu, Jinfeng | - |
dc.contributor.author | Bhatt, Parva K. | - |
dc.contributor.author | Monette, Sebastien | - |
dc.contributor.author | Zhao, Xinyang | - |
dc.contributor.author | Mason, Christopher E. | - |
dc.contributor.author | Park, Christopher Y. | - |
dc.contributor.author | Bernstein, Bradley E. | - |
dc.contributor.author | Aifantis, Iannis | - |
dc.contributor.author | Levine, Ross L. | - |
dc.date.accessioned | 2023-12-22T03:13:18Z | - |
dc.date.available | 2023-12-22T03:13:18Z | - |
dc.date.created | 2016-08-02 | - |
dc.date.issued | 2013-11 | - |
dc.description.abstract | Somatic Addition of Sex Combs Like 1 (ASXL1) mutations occur in 10-30% of patients with myeloid malignancies, most commonly in myelodysplastic syndromes (MDSs), and are associated with adverse outcome. Germline ASXL1 mutations occur in patients with Bohring-Opitz syndrome. Here, we show that constitutive loss of Asxl1 results in developmental abnormalities, including anophthalmia, microcephaly, cleft palates, and mandibular malformations. In contrast, hematopoietic-specific deletion of Asxl1 results in progressive, multilineage cytopenias and dysplasia in the context of increased numbers of hematopoietic stem/progenitor cells, characteristic features of human MDS. Serial transplantation of Asxl1-null hematopoietic cells results in a lethal myeloid disorder at a shorter latency than primary Asxl1 knockout (KO) mice. Asxl1 deletion reduces hematopoietic stem cell self-renewal, which is restored by concomitant deletion of Tet2, a gene commonly co-mutated with ASXL1 in MDS patients. Moreover, compound Asxl1/Tet2 deletion results in an MDS phenotype with hastened death compared with single-gene KO mice. Asxl1 loss results in a global reduction of H3K27 trimethylation and dysregulated expression of known regulators of hematopoiesis. RNA-Seq/ChIP-Seq analyses of Asxl1 in hematopoietic cells identify a subset of differentially expressed genes as direct targets of Asxl1. These findings underscore the importance of Asxl1 in Polycomb group function, development, and hematopoiesis | - |
dc.identifier.bibliographicCitation | JOURNAL OF EXPERIMENTAL MEDICINE, v.210, no.12, pp.2641 - 2659 | - |
dc.identifier.doi | 10.1084/jem.20131141 | - |
dc.identifier.issn | 0022-1007 | - |
dc.identifier.scopusid | 2-s2.0-84888116023 | - |
dc.identifier.uri | https://scholarworks.unist.ac.kr/handle/201301/20168 | - |
dc.identifier.url | http://jem.rupress.org/content/210/12/2641 | - |
dc.identifier.wosid | 000327446600012 | - |
dc.language | 영어 | - |
dc.publisher | ROCKEFELLER UNIV PRESS | - |
dc.title | Deletion of Asxl1 results in myelodysplasia and severe developmental defects in vivo | - |
dc.type | Article | - |
dc.description.journalRegisteredClass | scie | - |
dc.description.journalRegisteredClass | scopus | - |
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