scholarly journals Clinical significance of nuclear factor κB and chemokine receptor CXCR4 expression in patients with diffuse large B-cell lymphoma who received rituximab-based therapy

2014 ◽  
Vol 29 (6) ◽  
pp. 785 ◽  
Author(s):  
Ho Cheol Shin ◽  
Jongwon Seo ◽  
Byung Woog Kang ◽  
Joon Ho Moon ◽  
Yee Soo Chae ◽  
...  
2014 ◽  
Vol 134 (1) ◽  
pp. 290-292 ◽  
Author(s):  
Lianne Koens ◽  
Willem H. Zoutman ◽  
Passorn Ngarmlertsirichai ◽  
Grzegorz K. Przybylski ◽  
Piotr Grabarczyk ◽  
...  

2012 ◽  
Vol 53 (10) ◽  
pp. 1971-1977 ◽  
Author(s):  
Rong Bu ◽  
Prashant Bavi ◽  
Jehad Abubaker ◽  
Zeenath Jehan ◽  
Wael Al-Haqawi ◽  
...  

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. e18533-e18533
Author(s):  
Byung Woog Kang ◽  
Jong Gwang Kim ◽  
Yee Soo Chae ◽  
Soo Jung Lee ◽  
Sang Kyun Sohn ◽  
...  

e18533 Background: This study investigated the activation of nuclear factor kB (NFkB) and the chemokine receptor CXCR4 co-expression in patients with diffuse large B-cell lymphoma (DLBCL) who received rituximab-based therapy. Methods: Seventy patients with DLBCL and treated with rituximab-CHOP (RCHOP) were included. Tissue microarray blocks were created from 70 cases of DLBCL. Sections were stained with antibodies to IKKα, p-IkB, p50, p52, and CXCR4. To classify cases of DLBCL into GCB (germinal center B-cell-like) and non-GCB, additional immunohistochemical expression of CD10, bcl-6, or MUM1 has been used in this study. A numeric intensity score of 0-3 was assigned each case. Negative was scored if 0/+1 and positive was scored if 2+/3+. Results: The median age was 66.5 years (range, 17-87) and 58.6% were male. Twenty-seven patients (38.6%) had stage III and IV at diagnosis. Twenty-three patients (32.9%) were categorized as high or high-intermediate risk according to their IPI. The overall incidence of BM involvement was 5.7%. Positive expression for NFkB and CXCR4 were more than 80%. In NFkB and CXCR4 status, there are no significant difference between GCB and non-GCB. High NFkB expression is associated with CXCR4 expression and they are co-expressed in about two thirds of patients. With a median follow-up duration of 28.7 months (range, 0.1-76.1), the 5-year overall survival (OS) and event-free survival (EFS) rate was 67.4% and 79.8%, respectively. Neither NFkB nor CXCR4 were associated with DLBCL outcomes. Conclusions: In concolusion, none of the NFkB and CXCR4 expression profiles investigated in this study was found to be an independent prognostic marker for Korean patients with DLBCL. However, further studies on a larger scale are warranted to clarify the role of NFkB and CXCR4 as a prognostic marker.


Blood ◽  
2008 ◽  
Vol 111 (7) ◽  
pp. 3701-3713 ◽  
Author(s):  
Lloyd T. Lam ◽  
George Wright ◽  
R. Eric Davis ◽  
Georg Lenz ◽  
Pedro Farinha ◽  
...  

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.


2015 ◽  
Vol 46 (4) ◽  
pp. 524-531 ◽  
Author(s):  
Qian Zhao ◽  
Weijun Fu ◽  
Hua Jiang ◽  
Juan Du ◽  
Chunyang Zhang ◽  
...  

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