Mechanisms of NF-κB deregulation in lymphoid malignancies

Krappmann, Daniel; Vincendeau, Michelle

doi:10.1016/j.semcancer.2016.05.002

Cited by 25 publications

(22 citation statements)

References 135 publications

(178 reference statements)

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“…It appears that in HL, the aberrant activity of both NF-κB pathways is involved in the disease mechanism. The same appears to be the case for splenic marginal zone lymphomas and mucosal-associated lymphoid tissue (MALT) lymphomas [ 47 , 48 ] (Table 1).…”

Section: Aberrant Activation Of Nf-κb In Lymphoid Malignanciesmentioning

confidence: 59%

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Aberrant Activation of NF-κB Signalling in Aggressive Lymphoid Malignancies

Kennedy

Klein

2018

Cells

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Lymphoid malignancies frequently harbor genetic mutations leading to aberrant activation of nuclear factor-κB (NF-κB) signaling; in normal cells, this pathway has important roles in the control of cell growth, survival, stress responses, and inflammation. Malignancies with mutations in NF-κB pathway components can derive from all cell stages of mature B-cell development; however, aberrant NF-κB activity is particularly prevalent in aggressive subtypes of non-Hodgkin lymphoma and myeloma. NF-κB activation is mediated by two separate pathways, the canonical and alternative pathway, and five downstream transcription factor subunits. Recent findings implicate a predominant role for distinct NF-κB pathways and subunits in certain lymphoma subtypes and myeloma; findings which are complemented by the realization that individual NF-κB subunits can have unique, non-redundant biological roles in the putative tumor precursor cells, including activated B cells, germinal center B cells and plasma cells. The knowledge gained from these studies may be exploited for the development of therapeutic strategies to inhibit aberrant NF-κB activity at the level of the transcription-factor subunits and their target genes, as global inhibition of the pathway is toxic. Here, we provide an overview on the role of aberrant NF-κB activation in aggressive lymphoid malignancies and discuss the potential importance of individual NF-κB subunits in the pathogenesis of tumor subtypes.

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Section: Aberrant Activation Of Nf-κb In Lymphoid Malignanciesmentioning

confidence: 59%

“…Thereby, a special focus will be on MM and subtypes of aggressive B-NHL, where oncogenic NF-κB signaling due to genetic mutations is particularly prevalent. For a detailed discussion of the role of NF-κB in various lymphoma subtypes, we refer to excellent reviews [ 46 , 47 , 48 , 49 ].…”

Section: Aberrant Activation Of Nf-κb In Lymphoid Malignanciesmentioning

confidence: 99%

Aberrant Activation of NF-κB Signalling in Aggressive Lymphoid Malignancies

Kennedy

Klein

2018

Cells

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“…2c. NF-κB plays essential roles in the oncogenesis of various types of cancers and can provide antiapoptotic signals and promote proliferation 52 . KSHV-encoded vFLIP can activate NF-κB 53 .…”

Section: Resultsmentioning

confidence: 99%

Primary effusion lymphoma enhancer connectome links super-enhancers to dependency factors

Wang

Zhang

et al. 2020

Nat Commun

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Primary effusion lymphoma (PEL) has a very poor prognosis. To evaluate the contributions of enhancers/promoters interactions to PEL cell growth and survival, here we produce H3K27ac HiChIP datasets in PEL cells. This allows us to generate the PEL enhancer connectome, which links enhancers and promoters in PEL genome-wide. We identify more than 8000 genomic interactions in each PEL cell line. By incorporating HiChIP data with H3K27ac ChIP-seq data, we identify interactions between enhancers/enhancers, enhancers/promoters, and promoters/promoters. HiChIP further links PEL super-enhancers to PEL dependency factors MYC, IRF4, MCL1, CCND2, MDM2, and CFLAR. CRISPR knock out of MEF2C and IRF4 significantly reduces MYC and IRF4 super-enhancer H3K27ac signal. Knock out also reduces MYC and IRF4 expression. CRISPRi perturbation of these super-enhancers by tethering transcription repressors to enhancers significantly reduces target gene expression and reduces PEL cell growth. These data provide insights into PEL molecular pathogenesis.

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“…Under the action of IKK, IκBα is phosphorylated and then dissociated from p65/p50 dimer; p50 and p65 are dissociated into cytoplasm. Under the action of IKK and protein kinase A, p65 and p50 are phosphorylated, p-p65 and p-p50 into the nucleus, then exposing the nuclear localization sequence and binding to a specific DNA sequence [33,34]. e phosphorylation level of IκBα, p50, and p65 and the number of the p50 and p65 into the nucleus are the key to determine whether the classical NF-κB signaling pathway is activated or not.…”

Section: Discussionmentioning

confidence: 99%

trans‐Cinnamaldehyde Reverses Depressive‐Like Behaviors in Chronic Unpredictable Mild Stress Rats by Inhibiting NF‐κB/NLRP3 Inflammasome Pathway

Wang

Zhou

et al. 2020

Evidence-Based Complementary and Alternative Medicine

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trans-Cinnamaldehyde (TCA) is the main active component extracted from Cinnamomum cassia (C. cassia), which has many pharmacological effects, such as anti-inflammation, lowering blood glucose, and improving nerve function. However, there is no report of TCA in the treatment of depression. e purpose of this study was to investigate the antidepressant-like effect of TCA and the mechanism of NF kappa B (NF-κB) pathway and NLRP3 inflammasome inhibition by TCA. We divided 40 rats into the control group, CUMS group, FLU group, and the TCA group. e activation of the NF-κB pathway and NLRP3 inflammasome in prefrontal cortex and hippocampus of rats in each group was observed. After the treatments with FLU and TCA, the sucrose consumptions in rats increased significantly and the immobility time in forced swimming was decreased significantly compared to the CUMS group. e expression of TLR4, NF-κB-1, p-p65, TNF-α, NLRP3, ASC, caspase-1, IL-1β, and IL-18 proteins in prefrontal cortex and hippocampus was decreased, and the expression of IL-1β, IL-18, and TNF-α in serum was downregulated compared to the CUMS group. Similar to FLU, TCA reverses the depression-like behaviors in rats, which indicates that TCA has a significant antidepressant-like effect. e mechanism of the antidepressant property of TCA might be that it inhibits the activation of the NF-κB pathway and NLRP3 inflammasome in the prefrontal cortex and hippocampus of CUMS rats.

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Mechanisms of NF-κB deregulation in lymphoid malignancies

Cited by 25 publications

References 135 publications

Aberrant Activation of NF-κB Signalling in Aggressive Lymphoid Malignancies

Aberrant Activation of NF-κB Signalling in Aggressive Lymphoid Malignancies

Primary effusion lymphoma enhancer connectome links super-enhancers to dependency factors

trans‐Cinnamaldehyde Reverses Depressive‐Like Behaviors in Chronic Unpredictable Mild Stress Rats by Inhibiting NF‐κB/NLRP3 Inflammasome Pathway

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