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Study of the role of Wnt pathway in a murine model of T-ALL

Abstract : We report a murine model, R26-βcat, expressing a stable form of β-catenin in T cells. R26-βcat pre-leukemic mice show a developmental block in T-cell differentiation and exhibit increased resistance to apoptosis. Interestingly, the mice develop T cell lymphomas independent of the Notch pathway. Furthermore, we showed that loss of the tumour suppressor Pten and over-expression of Myc was favoured; and may constitute the secondary events contributing to this leukemogenesis. We also demonstrated that R26-βcat tumours are malignant, heterogeneous and that leukaemia stem cells (LSC) were enriched in DP cells. Furthermore, the self-renewal capapcity of R26-βcat LSCs can to be exhausted.We propose that the R26-βcat model defines a new sub-group of Notch-independent T-ALL and the β-catenin may serve as a potential therapeutic target for these tumours.
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Submitted on : Monday, December 2, 2013 - 1:09:06 AM
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Deepika Kaveri. Study of the role of Wnt pathway in a murine model of T-ALL. Biochemistry, Molecular Biology. Université de Strasbourg, 2012. English. ⟨NNT : 2012STRAJ061⟩. ⟨tel-00912330⟩

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