scholarly journals Nuclear Factor-κB Pathway–Activating Gene Aberrancies in Primary Cutaneous Large B-Cell Lymphoma, Leg Type

2014 ◽  
Vol 134 (1) ◽  
pp. 290-292 ◽  
Author(s):  
Lianne Koens ◽  
Willem H. Zoutman ◽  
Passorn Ngarmlertsirichai ◽  
Grzegorz K. Przybylski ◽  
Piotr Grabarczyk ◽  
...  
Keyword(s):  
B Cell ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Nuclear Factor Κb ◽  
Nuclear Factor ◽  
Large B Cell Lymphoma ◽  
Large B Cell

Role of nuclear factor-κB regulators TNFAIP3 and CARD11 in Middle Eastern diffuse large B-cell lymphoma

2012 ◽  
Vol 53 (10) ◽  
pp. 1971-1977 ◽  
Author(s):  
Rong Bu ◽  
Prashant Bavi ◽  
Jehad Abubaker ◽  
Zeenath Jehan ◽  
Wael Al-Haqawi ◽  
...  
Keyword(s):  
B Cell ◽  
Cell Lymphoma ◽  
Middle Eastern ◽  
B Cell Lymphoma ◽  
Nuclear Factor Κb ◽  
Nuclear Factor ◽  
Large B Cell Lymphoma ◽  
Large B Cell

scholarly journals Cooperative signaling through the signal transducer and activator of transcription 3 and nuclear factor-κB pathways in subtypes of diffuse large B-cell lymphoma

Blood ◽  
2008 ◽  
Vol 111 (7) ◽  
pp. 3701-3713 ◽  
Author(s):  
Lloyd T. Lam ◽  
George Wright ◽  
R. Eric Davis ◽  
Georg Lenz ◽  
Pedro Farinha ◽  
...  
Keyword(s):  
B Cell ◽  
Cell Lymphoma ◽  
Gene Expression Signature ◽  
B Cell Lymphoma ◽  
Nuclear Factor Κb ◽  
Janus Kinase ◽  
Nuclear Factor ◽  
Signal Transducer ◽  
Large B Cell Lymphoma ◽  
Large B Cell

Abstract The activated B cell–like (ABC) subgroup of diffuse large B-cell lymphoma (DLBCL) is characterized by constitutive activation of the nuclear factor-κB (NF-κB) pathway. In this study, we showed that the NF-κB pathway induced the expression of the cytokines interleukin (IL)-6 and IL-10 in ABC DLBCL cell lines, which also have high levels of total and phosphorylated signal transducer and activator of transcription (STAT) 3 protein, suggesting autocrine signaling. Using RNA interference for STAT3, we defined a gene expression signature of IL-6 and IL-10 signaling through STAT3. Based on this signature, we constructed a molecular predictor of STAT3 signaling that defined a subset of ABC DLBCL tumors with high expression of STAT3, IL-6, and/or IL-10 and their downstream targets. Although the STAT3-high and STAT3-low subsets had equivalent expression of genes that distinguish ABC DLBCL from germinal center B cell–like DLBCL, STAT3-high ABC DLBCLs had higher expression of signatures that reflected NF-κB activity, proliferation, and glycolysis. A small-molecule inhibitor of Janus kinase signaling, which blocked STAT3 signature expression, was toxic only for ABC DLBCL lines and synergized with an inhibitor of NF-κB signaling. These findings suggest that the biological interplay between the STAT3 and NF-κB pathways may be exploited for the treatments of a subset of ABC DLBCLs.

Clinicopathological implications of nuclear factor κB signal pathway activation in diffuse large B-cell lymphoma

2015 ◽  
Vol 46 (4) ◽  
pp. 524-531 ◽  
Author(s):  
Qian Zhao ◽  
Weijun Fu ◽  
Hua Jiang ◽  
Juan Du ◽  
Chunyang Zhang ◽  
...  
Keyword(s):  
B Cell ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Nuclear Factor Κb ◽  
Signal Pathway ◽  
Nuclear Factor ◽  
Large B Cell Lymphoma ◽  
Pathway Activation ◽  
Large B Cell

scholarly journals Constitutive Nuclear Factor κB Activity Is Required for Survival of Activated B Cell–like Diffuse Large B Cell Lymphoma Cells

2001 ◽  
Vol 194 (12) ◽  
pp. 1861-1874 ◽  
Author(s):  
R. Eric Davis ◽  
Keith D. Brown ◽  
Ulrich Siebenlist ◽  
Louis M. Staudt
Keyword(s):  
Gene Expression ◽  
B Cell ◽  
Gene Expression Profiling ◽  
Expression Profiling ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Nuclear Factor ◽  
Large B Cell Lymphoma ◽  
Dlbcl Subtype ◽  
Large B Cell

Gene expression profiling has revealed that diffuse large B cell lymphoma (DLBCL) consists of at least two distinct diseases. Patients with one DLBCL subtype, termed activated B cell–like (ABC) DLBCL, have a distinctly inferior prognosis. An untapped potential of gene expression profiling is its ability to identify pathogenic signaling pathways in cancer that are amenable to therapeutic attack. The gene expression profiles of ABC DLBCLs were notable for the high expression of target genes of the nuclear factor (NF)-κB transcription factors, raising the possibility that constitutive activity of the NF-κB pathway may contribute to the poor prognosis of these patients. Two cell line models of ABC DLBCL had high nuclear NF-κB DNA binding activity, constitutive IκB kinase (IKK) activity, and rapid IκBα degradation that was not seen in cell lines representing the other DLBCL subtype, germinal center B-like (GCB) DLBCL. Retroviral transduction of a super-repressor form of IκBα or dominant negative forms of IKKβ was toxic to ABC DLBCL cells but not GCB DLBCL cells. DNA content analysis showed that NF-κB inhibition caused both cell death and G1-phase growth arrest. These findings establish the NF-κB pathway as a new molecular target for drug development in the most clinically intractable subtype of DLBCL and demonstrate that the two DLBCL subtypes defined by gene expression profiling utilize distinct pathogenetic mechanisms.

scholarly journals EBV-positive diffuse large B-cell lymphoma of the elderly

Blood ◽  
2013 ◽  
Vol 122 (3) ◽  
pp. 328-340 ◽  
Author(s):  
Chi Young Ok ◽  
Thomas G. Papathomas ◽  
L. Jeffrey Medeiros ◽  
Ken H. Young
Keyword(s):  
B Cell ◽  
Cell Lymphoma ◽  
Low Frequency ◽  
B Cell Lymphoma ◽  
The Elderly ◽  
Nuclear Factor Κb ◽  
World Health ◽  
Barr Virus ◽  
Large B Cell Lymphoma ◽  
Large B Cell

Abstract Epstein-Barr virus (EBV) positive diffuse large B-cell lymphoma (DLBCL) of the elderly, initially described in 2003, is a provisional entity in the 2008 World Health Organization classification system and is defined as an EBV-positive monoclonal large B-cell proliferation that occurs in patients >50 years of age and in whom there is no known immunodeficiency or history of lymphoma. These tumors are more common in Asia but also occur in North America and Europe at a low frequency. These neoplasms exhibit a morphologic continuum, from polymorphous to monomorphous, but morphologic features do not correlate with prognosis as all patients have a clinically aggressive course. Most EBV-positive DLBCL of the elderly patients have an activated B-cell immunophenotype and are characterized by prominent nuclear factor-κB activation. Cytogenetic complexity is usually low. In this review, we comprehensively delineate the data emerging from analyses of EBV latency program, microRNA-mediated EBV viral oncogenesis, functional genomics of EBV and its biology, and differential diagnosis challenge for EBV-positive DLBCL of the elderly. It is hoped that the improved understanding of these tumors will lead to the development of novel therapeutic approaches, enhance the effectiveness of clinical trials, and improve prognosis.

Signal Pathways and Therapeutic Prospects of Diffuse Large B Cell Lymphoma

2020 ◽  
Vol 19 (17) ◽  
pp. 2047-2059
Author(s):  
Feifei Sun ◽  
Xiaosheng Fang ◽  
Xin Wang
Keyword(s):  
B Cell ◽  
Cell Lymphoma ◽  
Mammalian Target Of Rapamycin ◽  
B Cell Lymphoma ◽  
Nuclear Factor Κb ◽  
Janus Kinase ◽  
Signal Pathways ◽  
Non Hodgkin Lymphoma ◽  
Large B Cell Lymphoma ◽  
Large B Cell

Background: Diffuse Large B Cell Lymphoma (DLBCL) is the most common type of non-Hodgkin lymphoma which is heterogeneous both clinically and morphologically. Over the past decades, significant advances have been made in the understanding of the molecular genesis, leading to the identification of multiple pathways and molecules that can be targeted for clinical benefit. Objective: The current review aims to present a brief overview of signal pathways of DLBCL, which mainly focus on B-cell antigen Receptor (BCR), Nuclear Factor-κB (NF-κB), Phosphatidylinositol-3-Kinase (PI3K) – protein kinase B (Akt) – mammalian Target of Rapamycin (mTOR), Janus Kinase (JAK) – Signal Transducer and Activator (STAT), Wnt/β-catenin, and P53 pathways. Methods: Activation of signal pathways may contribute to the generation, development, chemotherapy sensitivity of DLBCL, and expression of pathway molecules is associated with the prognosis of DLBCL. Some agents targeting these pathways have been proved effective and relevant clinical trials are in progress. These agents used single or combined with chemotherapy/each other might raise the possibility of improving clinical outcomes in DLBCL. Conclusion: This review presents several signal pathways of DLBCL and targeted agents had a tendency to improve the curative effect, especially in high-risk or relapsed/refractory DLBCL.

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