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https://hdl.handle.net/2440/104500
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dc.contributor.author | Yu, S. | - |
dc.contributor.author | Zhou, X. | - |
dc.contributor.author | Steinke, F. | - |
dc.contributor.author | Liu, C. | - |
dc.contributor.author | Chen, S. | - |
dc.contributor.author | Zagorodna, O. | - |
dc.contributor.author | Jing, X. | - |
dc.contributor.author | Yokota, Y. | - |
dc.contributor.author | Meyerholz, D. | - |
dc.contributor.author | Mullighan, C. | - |
dc.contributor.author | Knudson, C. | - |
dc.contributor.author | Zhao, D. | - |
dc.contributor.author | Xue, H. | - |
dc.date.issued | 2012 | - |
dc.identifier.citation | Immunity, 2012; 37(5):813-826 | - |
dc.identifier.issn | 1074-7613 | - |
dc.identifier.issn | 1097-4180 | - |
dc.identifier.uri | http://hdl.handle.net/2440/104500 | - |
dc.description.abstract | The TCF-1 and LEF-1 transcription factors are known to play critical roles in normal thymocyte development. Unexpectedly, we found that TCF-1-deficient (Tcf7−/−) mice developed aggressive T cell malignancy, resembling human T cell acute lymphoblastic leukemia (T-ALL). LEF-1 was aberrantly upregulated in premalignant Tcf7−/− early thymocytes and lymphoma cells. We further demonstrated that TCF-1 directly repressed LEF-1 expression in early thymocytes and that conditional inactivation of Lef1 greatly delayed or prevented T cell malignancy in Tcf7−/− mice. In human T-ALLs, an early thymic progenitor (ETP) subtype was associated with diminished TCF7 expression, and two of the ETP-ALL cases harbored TCF7 gene deletions. We also showed that TCF-1 and LEF-1 were dispensable for T cell lineage commitment but instead were required for early thymocytes to mature beyond the CD4−CD8− stage. TCF-1 thus has dual roles, i.e., acting cooperatively with LEF-1 to promote thymocyte maturation while restraining LEF-1 expression to prevent malignant transformation of developing thymocytes. | - |
dc.description.statementofresponsibility | Shuyang Yu, Xinyuan Zhou, Farrah C. Steinke, Chengyu Liu, Shann-Ching Chen, Oksana Zagorodna, Xuefang Jing, Yoshifumi Yokota, David K. Meyerholz, Charles G. Mullighan, C. Michael Knudson, Dong-Mei Zhao and Hai-Hui Xue | - |
dc.language.iso | en | - |
dc.publisher | Cell Press | - |
dc.rights | ©2012 Elsevier Inc. | - |
dc.source.uri | http://dx.doi.org/10.1016/j.immuni.2012.08.009 | - |
dc.subject | Precursor T-Cell Lymphoblastic Leukemia-Lymphoma | - |
dc.title | The TCF-1 and LEF-1 transcription factors have cooperative and opposing roles in T cell development and malignancy | - |
dc.type | Journal article | - |
dc.identifier.doi | 10.1016/j.immuni.2012.08.009 | - |
pubs.publication-status | Published | - |
dc.identifier.orcid | Mullighan, C. [0000-0002-1871-1850] | - |
Appears in Collections: | Aurora harvest 3 Medicine publications |
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