NF-κB Mutations in Germinal Center B-Cell Lymphomas: Relation to NF-κB Function in Normal B Cells.
NF-κB Mutations in Germinal Center B-Cell Lymphomas: Relation to NF-κB Function in Normal B Cells.
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DOI：
10.3390/biomedicines10102450
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发表时间：
2022-10-01
期刊：
影响因子：
4.7
通讯作者：
中科院分区：
文献类型：
--
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大多数B细胞淋巴瘤是由经历T细胞依赖性免疫反应生发中心（GC）反应的B细胞的致瘤转化而产生的，在这个过程中产生高亲和力记忆B细胞和浆细胞。GC B细胞的高增殖加上体细胞超突变和类开关重组的dna修饰过程中偶尔出现的错误，使细胞处于获得转化遗传畸变的风险中，这可能激活原癌基因或使肿瘤抑制基因失活。一些亚型的GC淋巴瘤含有基因突变，导致核因子-κB （NF-κB）信号通路的组成性异常激活。在正常B细胞中，NF-κB在发育和生理中具有重要的生物学作用。GC淋巴瘤劫持这些活动，促进肿瘤细胞生长和存活。越来越清楚的是，NF-κB通路的典型和非典型途径以及下游5种NF-κB转录因子在GC - b细胞发育的各个阶段具有不同的功能。这些发现可能对理解异常的NF-κB活化如何促进各种GC淋巴瘤的发生具有直接意义，这些GC淋巴瘤对应于发育不同的GC b细胞亚群。从这些研究中获得的知识可以用于开发精确医学方法，旨在通过特异性NF-κB抑制剂更有效地治疗相应的肿瘤，从而降低全身毒性。我们在此概述了在各种GC淋巴瘤中遇到的NF-κB基因突变模式，并讨论了在这些恶性肿瘤中NF-κB异常活化与正常细胞中NF-κB生物学相关的后果。
Most B cell lymphomas arise from the oncogenic transformation of B cells that have undergone the germinal center (GC) reaction of the T cell-dependent immune response, where high-affinity memory B cells and plasma cells are generated. The high proliferation of GC B cells coupled with occasional errors in the DNA-modifying processes of somatic hypermutation and class switch recombination put the cell at a risk to obtain transforming genetic aberrations, which may activate proto-oncogenes or inactivate tumour suppressor genes. Several subtypes of GC lymphomas harbor genetic mutations leading to constitutive, aberrant activation of the nuclear factor-κB (NF-κB) signaling pathway. In normal B cells, NF-κB has crucial biological roles in development and physiology. GC lymphomas highjack these activities to promote tumour-cell growth and survival. It has become increasingly clear that the separate canonical and non-canonical routes of the NF-κB pathway and the five downstream NF-κB transcription factors have distinct functions in the successive stages of GC B-cell development. These findings may have direct implications for understanding how aberrant NF-κB activation promotes the genesis of various GC lymphomas corresponding to the developmentally distinct GC B-cell subsets. The knowledge arising from these studies may be explored for the development of precision medicine approaches aimed at more effective treatments of the corresponding tumours with specific NF-κB inhibitors, thus reducing systemic toxicity. We here provide an overview on the patterns of genetic NF-κB mutations encountered in the various GC lymphomas and discuss the consequences of aberrant NF-κB activation in those malignancies as related to the biology of NF-κB in their putative normal cellular counterparts.
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影响因子：
50.3
作者：
Calado DP;Zhang B;Srinivasan L;Sasaki Y;Seagal J;Unitt C;Rodig S;Kutok J;Tarakhovsky A;Schmidt-Supprian M;Rajewsky K
通讯作者：
Rajewsky K
影响因子：
20.3
作者：
Chu, Yuanyuan;Vahl, J. Christoph;Schmidt-Supprian, Marc
通讯作者：
Schmidt-Supprian, Marc
DOI：
10.1073/pnas.1921187117
发表时间：
2020-03-17
影响因子：
11.1
作者：
Choi, Jaewoo;Phelan, James D.;Staudt, Louis M.
通讯作者：
Staudt, Louis M.
影响因子：
20.3
作者：
Chapuy, Bjoern;Stewart, Chip;Shipp, Margaret A.
通讯作者：
Shipp, Margaret A.
影响因子：
20.3
作者：
Basso, K;Klein, U;Dalla-Favera, R
通讯作者：
Dalla-Favera, R