Prognostic impact of C-REL expression in diffuse large B-cell lymphoma

Curry, Choladda V.; Ewton, April A.; Olsen, Randall J.; Logan, Brent R.; Preti, Hector Alejandro; Liu, Yao Chang; Perkins, Sherrie L.; Chang, Chung Che

doi:10.1007/s12308-009-0021-4

Cited by 25 publications

(24 citation statements)

References 26 publications

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“…Curry et al 15 showed a worse OS in patients with c-Rel + GCB-DLBCL compared with that in patients with c-Rel − GCB-DLBCL. 15 Espinosa et al reported better outcome in patients with phosphorylated p65 + DLBCL compared with that in patients with p65 − DLBCL. 9 However, patients in these two studies were treated with chemotherapy without rituximab.…”

Section: Discussionmentioning

confidence: 97%

“…Moreover, most previous studies have evaluated only a subset of the NF-κB subunits. [8][9][10][11][12][13][14][15] There are only two studies using all five subunits in DLBCL-a cohort of 88 patients with DLBCL by Odqvist et al 16 and a cohort of 45 patients with testicular DLBCL by Menter et al 17 In the current study, we evaluated expression of all five subunits of the NF-κB protein by immunohistochemistry and its clinical implications in a large cohort of patients with de novo DLBCL.…”

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confidence: 98%

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Evaluation of NF-κB subunit expression and signaling pathway activation demonstrates that p52 expression confers better outcome in germinal center B-cell-like diffuse large B-cell lymphoma in association with CD30 and BCL2 functions

Xu-Monette

et al. 2015

Modern Pathology

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Nuclear factor-κB (NF-κB) is a transcription factor with a well-described oncogenic role. Study for each of five NF-κB pathway subunits was only reported on small cohorts in diffuse large B-cell lymphoma (DLBCL). In this large cohort (n = 533) of patients with de novo DLBCL, we evaluated the protein expression frequency, gene expression signature, and clinical implication for each of these five NF-κB subunits. Expression of p50, p52, p65, RELB, and c-Rel was 34%, 12%, 20%, 14%, and 23%, whereas p50/p65, p50/c-Rel, and p52/RELB expression was 11%, 11%, and 3%, respectively. NF-κB subunits were expressed in both germinal center B-cell-like (GCB) and activated B-cell-like (ABC) DLBCL, but p50 and p50/c-Rel were associated with ABC-DLBCL. p52, RELB, and p52/ RELB expressions were associated with CD30 expression. p52 expression was negatively associated with BCL2 (B-cell lymphoma 2) expression and BCL2 rearrangement. Although p52 expression was associated with better progression-free survival (PFS) (P = 0.0170), singular expression of the remaining NF-κB subunits alone did not show significant prognostic impact in the overall DLBCL cohort. Expression of p52/RELB was associated with better overall survival (OS) and PFS (P = 0.0307 and P = 0.0247). When cases were stratified into GCB-and

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Section: Discussionmentioning

confidence: 97%

mentioning

confidence: 98%

Evaluation of NF-κB subunit expression and signaling pathway activation demonstrates that p52 expression confers better outcome in germinal center B-cell-like diffuse large B-cell lymphoma in association with CD30 and BCL2 functions

Xu-Monette

et al. 2015

Modern Pathology

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“…20 Moreover, nuclear REL assessed by immunohistochemistry, was associated with worse clinical outcome in GCB DLBCL in a previous publication. 29 Those studies though were performed in biopsies from patients treated with chemotherapy without rituximab. As the addition of rituximab has markedly improved the overall survival rates in DLBCL, and the outcome of survival analyses depends on the clinical management, this can be a possible explanation for the observed differences.…”

Section: Discussionmentioning

confidence: 99%

NFκB expression is a feature of both activated B-cell-like and germinal center B-cell-like subtypes of diffuse large B-cell lymphoma

et al. 2014

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The activation of nuclear factor kappa B (NFjB) transcription factor family is considered to have a key role in diffuse large B-cell lymphoma (DLBCL) pathogenesis and is associated with a specific molecular subtype, the activated B-cell-like (ABC) subtype. We evaluated the expression of NFjB by immunohistochemistry in a large series of DLBCL cases. The five different NFjB family members (NFjB1, NFjB2, RELA, RELB, and REL) showed a heterogeneous expression pattern with the vast majority of cases being positive for at least one factor. Two independent series of tumor samples were classified into germinal center B-cell-like (GCB) or ABC subtypes using different approaches, immunohistochemistry, or gene expression profiling, and the expression of NFjB family members was assessed. Notably, no significant differences regarding the expression of the different NFjB members were detected between the two subtypes, suggesting that NFjB signaling is a prominent feature not only in the ABC subtype, but also in the GCB tumors. Of the five transcription factors, only REL expression had a significant clinical impact on R-CHOP-treated diffuse large B-cell lymphoma, identifying a subgroup of patients with superior clinical outcome. Diffuse large B-cell lymphoma (DLBCL) is the most common type of lymphoma in adults and is clinically and molecularly a heterogeneous disease. 1,2 Based on gene expression profiling, two different molecular subtypes of DLBCL were recognized according to the putative cell of origin; the more aggressive activated B-cell-like (ABC) subtype and the germinal center B-cell-like (GCB) subtype. [3][4][5] These subtypes reflect distinct differentiation stages of normal B-cell development and differ in their clinical presentation, cure rates, and molecular features. 2 Due to practical reasons, algorithms to classify these subtypes using immunohistochemistry of a few markers instead of gene expression profiling have been developed and extensively used. 6,7 These subtypes differ in their oncogenic programs and several subtype-specific genetic alterations have been described. 2,8,9 A hallmark of the ABC subtype is constitutive nuclear factor kappa B (NFkB) activation, and a disruption of this activation induces apoptosis in ABC cell lines. 10 Several recurrent genetic aberrations affecting NFkB signaling have been described in the ABC tumors, including for instance mutations in caspase recruitment

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“…In ABC-DLBCL, dysregulation of the NF-κB canonical and non-canonical pathways is associated with inferior prognosis [123, 125]. In GCB-DLBCL, patients with P52+ and P52+/RelB+ which activate the non-canonical pathway are associated with better overall survival and progressive-free survival than patients with P52- and P52-/RelB- [123]; A worse overall survival occurs in patients with c-Rel+ DLBCL, associated with the canonical pathway, compared with the survival of patients c-Rel-tumors [126]. However, there are heterogeneous expression patterns in many patients and there are no well characterized studies correlating each of these subtypes.…”

Section: Nf-κb Pathway and Different Types Of Lymphomamentioning

confidence: 99%

NF-κB signaling pathway and its potential as a target for therapy in lymphoid neoplasms

Medeiros

et al. 2017

Blood Reviews

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The NF-κB pathway, a critical regulator of apoptosis, plays a key role in many normal cellular functions. Genetic alterations and other mechanisms leading to constitutive activation of the NF-κB pathway contribute to cancer development, progression and therapy resistance by activation of downstream anti-apoptotic pathways, unfavorable microenvironment interactions, and gene dysregulation. Not surprisingly, given its importance to normal and cancer cell function, the NF-κB pathway has emerged as a target for therapy. In the review, we present the physiologic role of the NF-κB pathway and recent advances in better understanding of the pathologic roles of the NF-κB pathway in major types of lymphoid neoplasms. We also provide an update of clinical trials that use NF-κB pathway inhibitors. These trials are exploring the clinical efficiency of combining NF-κB pathway inhibitors with various agents that target diverse mechanisms of action with the goal being to optimize novel therapeutic opportunities for targeting oncogenic pathways to eradicate cancer cells.

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Prognostic impact of C-REL expression in diffuse large B-cell lymphoma

Cited by 25 publications

References 26 publications

Evaluation of NF-κB subunit expression and signaling pathway activation demonstrates that p52 expression confers better outcome in germinal center B-cell-like diffuse large B-cell lymphoma in association with CD30 and BCL2 functions

Evaluation of NF-κB subunit expression and signaling pathway activation demonstrates that p52 expression confers better outcome in germinal center B-cell-like diffuse large B-cell lymphoma in association with CD30 and BCL2 functions

NFκB expression is a feature of both activated B-cell-like and germinal center B-cell-like subtypes of diffuse large B-cell lymphoma

NF-κB signaling pathway and its potential as a target for therapy in lymphoid neoplasms

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