Academic Journal
Overexpression of Lmo2 initiates T-lymphoblastic leukemia via impaired thymocyte competition
| العنوان: | Overexpression of Lmo2 initiates T-lymphoblastic leukemia via impaired thymocyte competition |
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| المؤلفون: | Abdulla, HDD, Alserihi, R, Flensburg, C, Abeysekera, W, Luo, M-X, Gray, DHD, Liu, X, Smyth, GKK, Alexander, WSS, Majewski, IJJ, McCormack, MPP |
| بيانات النشر: | ROCKEFELLER UNIV PRESS |
| سنة النشر: | 2023 |
| المجموعة: | The University of Melbourne: Digital Repository |
| الوصف: | Cell competition has recently emerged as an important tumor suppressor mechanism in the thymus that inhibits autonomous thymic maintenance. Here, we show that the oncogenic transcription factor Lmo2 causes autonomous thymic maintenance in transgenic mice by inhibiting early T cell differentiation. This autonomous thymic maintenance results in the development of self-renewing preleukemic stem cells (pre-LSCs) and subsequent leukemogenesis, both of which are profoundly inhibited by restoration of thymic competition or expression of the antiapoptotic factor BCL2. Genomic analyses revealed the presence of Notch1 mutations in pre-LSCs before subsequent loss of tumor suppressors promotes the transition to overt leukemogenesis. These studies demonstrate a critical role for impaired cell competition in the development of pre-LSCs in a transgenic mouse model of T cell acute lymphoblastic leukemia (T-ALL), implying that this process plays a role in the ontogeny of human T-ALL. |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| تدمد: | 0022-1007 1540-9538 |
| Relation: | NHMRC/1003391; pii: 213937; Abdulla, H. D. D., Alserihi, R., Flensburg, C., Abeysekera, W., Luo, M. -X., Gray, D. H. D., Liu, X., Smyth, G. K. K., Alexander, W. S. S., Majewski, I. J. J. & McCormack, M. P. P. (2023). Overexpression of Lmo2 initiates T-lymphoblastic leukemia via impaired thymocyte competition. JOURNAL OF EXPERIMENTAL MEDICINE, 220 (6), https://doi.org/10.1084/jem.20212383.; http://hdl.handle.net/11343/333142 |
| الاتاحة: | http://hdl.handle.net/11343/333142 |
| Rights: | CC BY-NC-SA ; https://creativecommons.org/licenses/by-nc-sa/4.0 |
| رقم الانضمام: | edsbas.7B89CFCD |
| قاعدة البيانات: | BASE |
Full Text Finder | تدمد: | 00221007 15409538 |
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