dc.contributor.author | Jaenisch, Rudolf | |
dc.contributor.author | Huang, Hao | |
dc.contributor.author | Jiang, Xi | |
dc.contributor.author | Li, Zejuan | |
dc.contributor.author | Li, Yuanyuan | |
dc.contributor.author | Song, Chun-Xiao | |
dc.contributor.author | He, Chunjiang | |
dc.contributor.author | Chen, Ping | |
dc.contributor.author | Gurbuxani, Sandeep | |
dc.contributor.author | Wang, Jiapeng | |
dc.contributor.author | Hong, Gia-Ming | |
dc.contributor.author | Elkahloun, Abdel G. | |
dc.contributor.author | Arnovitz, Stephen | |
dc.contributor.author | Wang, Jinhua | |
dc.contributor.author | Szulwach, Keith | |
dc.contributor.author | Lin, Li | |
dc.contributor.author | Street, Craig | |
dc.contributor.author | Wunderlich, Mark | |
dc.contributor.author | Dawlaty, Meelad M. | |
dc.contributor.author | Neilly, Mary Beth | |
dc.contributor.author | Yang, Feng-Chun | |
dc.contributor.author | Mulloy, James C. | |
dc.contributor.author | Jin, Peng | |
dc.contributor.author | Liu, Paul P. | |
dc.contributor.author | Rowley, Janet D. | |
dc.contributor.author | Xu, Mingjiang | |
dc.contributor.author | He, Chuan | |
dc.contributor.author | Chen, Jianjun | |
dc.contributor.author | Sun, Miao, M. Eng. Massachusetts Institute of Technology | |
dc.date.accessioned | 2014-03-24T16:36:58Z | |
dc.date.available | 2014-03-24T16:36:58Z | |
dc.date.issued | 2013-07 | |
dc.date.submitted | 2013-05 | |
dc.identifier.issn | 0027-8424 | |
dc.identifier.issn | 1091-6490 | |
dc.identifier.uri | http://hdl.handle.net/1721.1/85907 | |
dc.description.abstract | The ten-eleven translocation 1 (TET1) gene is the founding member of the TET family of enzymes (TET1/2/3) that convert 5-methylcytosine to 5-hydroxymethylcytosine. Although TET1 was first identified as a fusion partner of the mixed lineage leukemia (MLL) gene in acute myeloid leukemia carrying t(10,11), its definitive role in leukemia is unclear. In contrast to the frequent down-regulation (or loss-of-function mutations) and critical tumor-suppressor roles of the three TET genes observed in various types of cancers, here we show that TET1 is a direct target of MLL-fusion proteins and is significantly up-regulated in MLL-rearranged leukemia, leading to a global increase of 5-hydroxymethylcytosine level. Furthermore, our both in vitro and in vivo functional studies demonstrate that Tet1 plays an indispensable oncogenic role in the development of MLL-rearranged leukemia, through coordination with MLL-fusion proteins in regulating their critical cotargets, including homeobox A9 (Hoxa9)/myeloid ecotropic viral integration 1 (Meis1)/pre-B-cell leukemia homeobox 3 (Pbx3) genes. Collectively, our data delineate an MLL-fusion/Tet1/Hoxa9/Meis1/Pbx3 signaling axis in MLL-rearranged leukemia and highlight TET1 as a potential therapeutic target in treating this presently therapy-resistant disease. | en_US |
dc.language.iso | en_US | |
dc.publisher | National Academy of Sciences (U.S.) | en_US |
dc.relation.isversionof | http://dx.doi.org/10.1073/pnas.1310656110 | en_US |
dc.rights | Article is made available in accordance with the publisher's policy and may be subject to US copyright law. Please refer to the publisher's site for terms of use. | en_US |
dc.source | National Academy of Science (U.S.) | en_US |
dc.title | TET1 plays an essential oncogenic role in MLL-rearranged leukemia | en_US |
dc.type | Article | en_US |
dc.identifier.citation | Huang, H., X. Jiang, Z. Li, Y. Li, C.-X. Song, C. He, M. Sun, et al. “TET1 Plays an Essential Oncogenic Role in MLL-Rearranged Leukemia.” Proceedings of the National Academy of Sciences 110, no. 29 (July 16, 2013): 11994–11999. | en_US |
dc.contributor.department | Massachusetts Institute of Technology. Department of Biology | en_US |
dc.contributor.department | Whitehead Institute for Biomedical Research | en_US |
dc.contributor.mitauthor | Jaenisch, Rudolf | en_US |
dc.relation.journal | Proceedings of the National Academy of Sciences | en_US |
dc.eprint.version | Final published version | en_US |
dc.type.uri | http://purl.org/eprint/type/JournalArticle | en_US |
eprint.status | http://purl.org/eprint/status/PeerReviewed | en_US |
dspace.orderedauthors | Huang, H.; Jiang, X.; Li, Z.; Li, Y.; Song, C.-X.; He, C.; Sun, M.; Chen, P.; Gurbuxani, S.; Wang, J.; Hong, G.-M.; Elkahloun, A. G.; Arnovitz, S.; Wang, J.; Szulwach, K.; Lin, L.; Street, C.; Wunderlich, M.; Dawlaty, M.; Neilly, M. B.; Jaenisch, R.; Yang, F.-C.; Mulloy, J. C.; Jin, P.; Liu, P. P.; Rowley, J. D.; Xu, M.; He, C.; Chen, J. | en_US |
mit.license | PUBLISHER_POLICY | en_US |
mit.metadata.status | Complete | |