NF-kB and the CLL microenvironment.pdf (2.47 MB)
NF-kB and the CLL microenvironment
journal contribution
posted on 2023-06-10, 07:07 authored by Alice O’Donnell, Christopher PepperChristopher Pepper, Simon MitchellSimon Mitchell, Andrea PepperAndrea PepperChronic lymphocytic leukemia (CLL) is the most prevalent type of leukemia in the western world. Despite the positive clinical effects of new targeted therapies, CLL still remains an incurable and refractory disease and resistance to treatments are commonly encountered. The Nuclear Factor-Kappa B (NF-?B) transcription factor has been implicated in the pathology of CLL, with high levels of NF-?B associated with disease progression and drug resistance. This aberrant NF-?B activation can be caused by genetic mutations in the tumor cells and microenvironmental factors, which promote NF-?B signaling. Activation can be induced via two distinct pathways, the canonical and non-canonical pathway, which result in tumor cell proliferation, survival and drug resistance. Therefore, understanding how the CLL microenvironment drives NF-?B activation is important for deciphering how CLL cells evade treatment and may aid the development of novel targeting therapeutics. The CLL microenvironment is comprised of various cells, including nurse like cells, mesenchymal stromal cells, follicular dendritic cells and CD4+ T cells. By activating different receptors, including the B cell receptor and CD40, these cells cause overactivity of the canonical and non-canonical NF-?B pathways. Within this review, we will explore the different components of the CLL microenvironment that drive the NF-?B pathway, investigating how this knowledge is being translated in the development of new therapeutics.
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Publication status
- Published
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- Published version
Journal
Frontiers in OncologyISSN
2234-943XPublisher
Frontiers Media SAExternal DOI
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13Page range
a1169397 1-9Event location
SwitzerlandDepartment affiliated with
- Clinical and Experimental Medicine Publications
Full text available
- Yes
Peer reviewed?
- Yes
Legacy Posted Date
2023-05-23First Open Access (FOA) Date
2023-05-23First Compliant Deposit (FCD) Date
2023-05-22Usage metrics
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