NF-kB and the CLL microenvironment

Frontiers in Oncology

Oncology

Chris Pepper¹  Simon Mitchell¹  Andrea Pepper¹  Alice O’Donnell² 

[1] Department of Clinical and Experimental Medicine, Brighton and Sussex Medical School, Brighton, United Kingdom;Department of Clinical and Experimental Medicine, Brighton and Sussex Medical School, Brighton, United Kingdom;Royal Sussex County Hospital, University Hospitals Sussex, Brighton, United Kingdom;

关键词: chronic lymphocytic leukemia;    NF-kappaB signaling pathway;    tumor microenvironment;    hematological malignancies;    therapeutic targets;    CLL;   

DOI  :  10.3389/fonc.2023.1169397

 received in 2023-02-19, accepted in 2023-03-20,  发布年份 2023

来源: Frontiers

【 摘 要 】

Chronic 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-κB) transcription factor has been implicated in the pathology of CLL, with high levels of NF-κB associated with disease progression and drug resistance. This aberrant NF-κB activation can be caused by genetic mutations in the tumor cells and microenvironmental factors, which promote NF-κB 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-κB 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-κB pathways. Within this review, we will explore the different components of the CLL microenvironment that drive the NF-κB pathway, investigating how this knowledge is being translated in the development of new therapeutics.

【 授权许可】

Unknown   
Copyright © 2023 O’Donnell, Pepper, Mitchell and Pepper