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| Status |
Public on Jan 01, 2022 |
| Title |
Lmo2 is dispensable for maintenance of most Lmo2-induced murine T-cell leukemias |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by array
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| Summary |
Lmo2 is an oncogenic transcription factor that is a frequent target of chromosomal abnormalities in this T-cell acute lymphoblastic leukemia (T-ALL). In transgenic mouse models, overexpression of Lmo2 causes thymocyte self-renewal leading to T-cell leukemia with long latency. However, the requirement of Lmo2 for maintenance of overt leukemia is poorly understood. We found that Lyl1, a critical cofactor for Lmo2-induced leukemia, is frequently lost in cell lines derived from Lmo2-transgenic mice, raising the possibility that Lmo2 function is dispensable at this stage. To study this, we developed a Tetracycline-repressible knock-in mouse model (Vav-TRE-Lmo2), which expresses Lmo2 throughout the haematopoietic system. This led to specific effects on T-cell development and the development of T-cell leukemia with long latency, preceded by the presence of self-renewing T-cells in the thymus. Repression of Lmo2 overcame the Lmo2-induced thymocyte developmental block at the preleukemic stage and led to elimination of Lmo2-induced thymocyte self-renewal in vivo. In contrast, Lmo2 function was dispensable for the majority of overt Lmo2-induced T-cell leukemias as well as leukemia-derived cell lines, implying an evolution of oncogene addiction in the majority of T-cell leukemias. Lmo2-dependence in T-ALL was associated with an immature gene expression profile, but could not be predicted by immunophenotype or assessment of Notch pathway activation. Thus, Lmo2 can give rise to both Lmo2-depenent and –independent T-cell leukemias. The Vav-TRE-Lmo2 model should be useful to determine the molecular features associated with Lmo2-dependence, as well as the critical components of the Lmo2-induced self-renewal pathways in T-ALL.
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| Overall design |
Transcriptome profiling of cell lines from T-cell leukemias arising in CD2-Lmo2 transgenic mice.
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| Contributor(s) |
Abdulla H, Davies TJ, Shi W, Shields BJ, McCormack MP |
| Citation missing |
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| Submission date |
Jan 25, 2019 |
| Last update date |
Jan 02, 2022 |
| Contact name |
Wei Shi |
| E-mail(s) |
Wei.Shi@onjcri.org.au
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| Organization name |
Olivia Newton-John Cancer Research Institute
|
| Street address |
145 Studley Road
|
| City |
Heidelberg |
| State/province |
Victoria |
| ZIP/Postal code |
3084 |
| Country |
Australia |
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| Platforms (1) |
| GPL6887 |
Illumina MouseWG-6 v2.0 expression beadchip |
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| Samples (9)
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| Relations |
| BioProject |
PRJNA517144 |
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