| BORDINI, Jessica, Chiara LENZI, Michela FRENQUELLI, Alessia MORABITO, Athanasios PSEFTOGAS, Daniela BELLONI, Larry MANSOURI, George TSIOLAS, Eleonora PEROTTA, Pamela RANGHETTI, Francesca GANDINI, Francesca GENOVA, Daniel HAGERSTRAND, Georgios GAVRIILIDIS, Sofoklis KEISARIS, Nikolaos PECHLIVANIS, Frederic DAVI, Neil E KAY, Anton W LANGERAK, Šárka POSPÍŠILOVÁ, Lydia SCARFO, Antonios MAKRIS, Fotis E PSOMOPOULOS, Kostas STAMATOPOULOS, Richard ROSENQUIST, Alessandro CAMPANELLA a Paolo GHIA. IκBε deficiency accelerates disease development in chronic lymphocytic leukemia. Leukemia. London: Nature Publishing Group, 2024, 12 s. ISSN 0887-6924. Dostupné z: https://dx.doi.org/10.1038/s41375-024-02236-4. |
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@article{2409794,
author = {Bordini, Jessica and Lenzi, Chiara and Frenquelli, Michela and Morabito, Alessia and Pseftogas, Athanasios and Belloni, Daniela and Mansouri, Larry and Tsiolas, George and Perotta, Eleonora and Ranghetti, Pamela and Gandini, Francesca and Genova, Francesca and Hagerstrand, Daniel and Gavriilidis, Georgios and Keisaris, Sofoklis and Pechlivanis, Nikolaos and Davi, Frederic and Kay, Neil E and Langerak, Anton W and Pospíšilová, Šárka and Scarfo, Lydia and Makris, Antonios and Psomopoulos, Fotis E and Stamatopoulos, Kostas and Rosenquist, Richard and Campanella, Alessandro and Ghia, Paolo},
article_location = {London},
doi = {http://dx.doi.org/10.1038/s41375-024-02236-4},
keywords = {chronic lymphocytic leukemia; IκBε deficiency},
language = {eng},
issn = {0887-6924},
journal = {Leukemia},
title = {IκBε deficiency accelerates disease development in chronic lymphocytic leukemia},
url = {https://www.nature.com/articles/s41375-024-02236-4},
year = {2024}
}
TY - JOUR
ID - 2409794
AU - Bordini, Jessica - Lenzi, Chiara - Frenquelli, Michela - Morabito, Alessia - Pseftogas, Athanasios - Belloni, Daniela - Mansouri, Larry - Tsiolas, George - Perotta, Eleonora - Ranghetti, Pamela - Gandini, Francesca - Genova, Francesca - Hagerstrand, Daniel - Gavriilidis, Georgios - Keisaris, Sofoklis - Pechlivanis, Nikolaos - Davi, Frederic - Kay, Neil E - Langerak, Anton W - Pospíšilová, Šárka - Scarfo, Lydia - Makris, Antonios - Psomopoulos, Fotis E - Stamatopoulos, Kostas - Rosenquist, Richard - Campanella, Alessandro - Ghia, Paolo
PY - 2024
TI - IκBε deficiency accelerates disease development in chronic lymphocytic leukemia
JF - Leukemia
PB - Nature Publishing Group
SN - 08876924
KW - chronic lymphocytic leukemia
KW - IκBε deficiency
UR - https://www.nature.com/articles/s41375-024-02236-4
N2 - The NFKBIE gene, which encodes the NF-kappa B inhibitor I kappa B epsilon, is mutated in 3-7% of patients with chronic lymphocytic leukemia (CLL). The most recurrent alteration is a 4-bp frameshift deletion associated with NF-kappa B activation in leukemic B cells and poor clinical outcome. To study the functional consequences of NFKBIE gene inactivation, both in vitro and in vivo, we engineered CLL B cells and CLL-prone mice to stably down-regulate NFKBIE expression and investigated its role in controlling NF-kappa B activity and disease expansion. We found that I kappa B epsilon loss leads to NF-kappa B pathway activation and promotes both migration and proliferation of CLL cells in a dose-dependent manner. Importantly, NFKBIE inactivation was sufficient to induce a more rapid expansion of the CLL clone in lymphoid organs and contributed to the development of an aggressive disease with a shortened survival in both xenografts and genetically modified mice. I kappa B epsilon deficiency was associated with an alteration of the MAPK pathway, also confirmed by RNA-sequencing in NFKBIE-mutated patient samples, and resistance to the BTK inhibitor ibrutinib. In summary, our work underscores the multimodal relevance of the NF-kappa B pathway in CLL and paves the way to translate these findings into novel therapeutic options.
ER -
BORDINI, Jessica, Chiara LENZI, Michela FRENQUELLI, Alessia MORABITO, Athanasios PSEFTOGAS, Daniela BELLONI, Larry MANSOURI, George TSIOLAS, Eleonora PEROTTA, Pamela RANGHETTI, Francesca GANDINI, Francesca GENOVA, Daniel HAGERSTRAND, Georgios GAVRIILIDIS, Sofoklis KEISARIS, Nikolaos PECHLIVANIS, Frederic DAVI, Neil E KAY, Anton W LANGERAK, Šárka POSPÍŠILOVÁ, Lydia SCARFO, Antonios MAKRIS, Fotis E PSOMOPOULOS, Kostas STAMATOPOULOS, Richard ROSENQUIST, Alessandro CAMPANELLA a Paolo GHIA. IκBε deficiency accelerates disease development in chronic lymphocytic leukemia. \textit{Leukemia}. London: Nature Publishing Group, 2024, 12 s. ISSN~0887-6924. Dostupné z: https://dx.doi.org/10.1038/s41375-024-02236-4.
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