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https://hdl.handle.net/2440/104500
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Type: | Journal article |
Title: | The TCF-1 and LEF-1 transcription factors have cooperative and opposing roles in T cell development and malignancy |
Author: | Yu, S. Zhou, X. Steinke, F. Liu, C. Chen, S. Zagorodna, O. Jing, X. Yokota, Y. Meyerholz, D. Mullighan, C. Knudson, C. Zhao, D. Xue, H. |
Citation: | Immunity, 2012; 37(5):813-826 |
Publisher: | Cell Press |
Issue Date: | 2012 |
ISSN: | 1074-7613 1097-4180 |
Statement of Responsibility: | 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 |
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. |
Keywords: | Precursor T-Cell Lymphoblastic Leukemia-Lymphoma |
Rights: | ©2012 Elsevier Inc. |
DOI: | 10.1016/j.immuni.2012.08.009 |
Published version: | http://dx.doi.org/10.1016/j.immuni.2012.08.009 |
Appears in Collections: | Aurora harvest 3 Medicine publications |
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