Deletion of NF-κB/p50 influences the outcome of Notch3-dependent T cell leukemia (63.4)
| Autor: | Antonio Campese, Paola Grazioli, Gaia Scafetta, Claudia Noce, Sofia Verkhovskaia, Chiara Mari, Mari Pia Felli, Alberto Gulino, Isabella Screpanti |
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| Rok vydání: | 2012 |
| Předmět: | |
| Zdroj: | The Journal of Immunology. 188:63.4-63.4 |
| ISSN: | 1550-6606 0022-1767 |
| DOI: | 10.4049/jimmunol.188.supp.63.4 |
| Popis: | The deregulation of Notch3 signaling inside T-cell compartment of transgenic (N3-tg) mice, induces an aggressive form of T-cell acute lymphoblastic lymphoma (T-ALL), sustained by a constitutive activation of the NF-κB canonical pathway, mainly represented by the p50/p65 heterodimer. To clarify the Notch/NF-κB relationships in the development of T-ALL, we generated double mutant mice, deleted of the NF-κB/p50 subunit in a Notch3 transgenic background (N3-tg/p50-/-). The follow-up of N3-tg/p50-/- versus N3-tg mice revealed that p50 deletion strongly inhibits the development of Notch3-dependent T-ALL. Surprisingly, double mutant succumb earlier than N3-tg mice, displaying the trait of a myeloproliferative disease, with an aberrant accumulation of Mac1+Gr1+ myeloid cells in both spleen and peripheral blood, as well as of granulocyte/monocyte progenitors in the bone marrow. Our preliminary results suggest that Notch3 overexpression in T-cell compartment is able to influence, possibly in trans, the equilibrium of the myeloid compartment and that the ablation of NF-κB canonical pathway may impact on the outcomes of a T-cell specific deregulation of Notch signaling. We provide a useful experimental model to extend our understanding of Notch/NF-κB interplay in hemopoietic system and to unravel novel relationships between lymphoid and myeloid differentiation. |
| Databáze: | OpenAIRE |
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