NF-kB and the CLL microenvironment.
NF-kB and the CLL microenvironment.
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DOI：
10.3389/fonc.2023.1169397
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发表时间：
2023
影响因子：
4.7
通讯作者：
Pepper, Andrea
中科院分区：
文献类型：
--
作者：
O'Donnell, Alice;Pepper, Chris;Mitchell, Simon;Pepper, Andrea
关键词：
慢性淋巴细胞白血病（CLL）是西方世界最常见的白血病类型。尽管新的靶向治疗具有积极的临床效果，但CLL仍然是一种不可治愈的难治性疾病，并且通常会遇到对治疗的耐药性。核因子-κ B（NF-κB）转录因子与CLL的病理学有关，高水平的NF-κB与疾病进展和耐药性相关。这种异常的NF-κB激活可能是由肿瘤细胞中的基因突变和微环境因素引起的，其促进NF-κB信号传导。活化可以通过两种不同的途径诱导，即经典途径和非经典途径，其导致肿瘤细胞增殖、存活和耐药性。因此，了解CLL微环境如何驱动NF-κB活化对于解释CLL细胞如何逃避治疗是重要的，并且可能有助于开发新的靶向治疗剂。CLL微环境由各种细胞组成，包括护士样细胞、间充质基质细胞、滤泡树突状细胞和CD 4 + T细胞。通过激活不同的受体，包括B细胞受体和CD 40，这些细胞导致经典和非经典NF-κB途径的过度活性。在这篇综述中，我们将探讨CLL微环境中驱动NF-κB通路的不同组分，研究这些知识如何在新疗法的开发中被转化。
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.
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影响因子：
8.8
作者：
Almaden JV;Tsui R;Liu YC;Birnbaum H;Shokhirev MN;Ngo KA;Davis-Turak JC;Otero D;Basak S;Rickert RC;Hoffmann A
通讯作者：
Hoffmann A
影响因子：
45.3
作者：
Caligaris-Cappio, Federico;Ghia, Paolo
通讯作者：
Ghia, Paolo
影响因子：
16.8
作者：
Bell, JK;Mullen, GED;Segal, DM
通讯作者：
Segal, DM
影响因子：
13
作者：
Basak, Soumen;Hoffmann, Alexander
通讯作者：
Hoffmann, Alexander
影响因子：
11.4
作者：
Benedetti, D.;Tissino, E.;Zucchetto, A.
通讯作者：
Zucchetto, A.