IκBε deficiency accelerates disease development in chronic lymphocytic leukemia
The result's identifiers
Result code in IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F65269705%3A_____%2F24%3A00079848" target="_blank" >RIV/65269705:_____/24:00079848 - isvavai.cz</a>
Alternative codes found
RIV/00216224:14110/24:00136209
Result on the web
<a href="https://www.nature.com/articles/s41375-024-02236-4" target="_blank" >https://www.nature.com/articles/s41375-024-02236-4</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.1038/s41375-024-02236-4" target="_blank" >10.1038/s41375-024-02236-4</a>
Alternative languages
Result language
angličtina
Original language name
IκBε deficiency accelerates disease development in chronic lymphocytic leukemia
Original language description
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.
Czech name
—
Czech description
—
Classification
Type
J<sub>imp</sub> - Article in a specialist periodical, which is included in the Web of Science database
CEP classification
—
OECD FORD branch
30205 - Hematology
Result continuities
Project
Result was created during the realization of more than one project. More information in the Projects tab.
Continuities
P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)<br>I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace
Others
Publication year
2024
Confidentiality
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů
Data specific for result type
Name of the periodical
Leukemia
ISSN
0887-6924
e-ISSN
1476-5551
Volume of the periodical
38
Issue of the periodical within the volume
6
Country of publishing house
US - UNITED STATES
Number of pages
12
Pages from-to
1287-1298
UT code for WoS article
001197088700001
EID of the result in the Scopus database
2-s2.0-85189466933