scholarly journals Constitutive NF-κB Activation Underlines Major Mechanism of Drug Resistance in Relapsed Refractory Diffuse Large B Cell Lymphoma

2015 ◽  
Vol 2015 ◽  
pp. 1-5 ◽  
Author(s):  
Francesco Turturro
Keyword(s):  
B Cell ◽  
Cell Lymphoma ◽  
Proteasome Inhibitors ◽  
B Cell Lymphoma ◽  
Novel Therapy ◽  
Major Mechanism ◽  
Molecular Abnormalities ◽  
Large B Cell Lymphoma ◽  
The Usa ◽  
Large B Cell

Diffuse large B cell lymphoma (DLBCL) is the most common subtype of B cell non-Hodgkin’s lymphoma (NHL), encompassing 30–40% of the estimated 70,000 cases of NHL in 2014 in the USA. Despite major improvements with immune-chemotherapy, the fraction of patients who still succumb to a refractory or relapsed disease remains high. This review addresses whether the better understanding of the biology of DLBCL defines new therapeutic avenues that may overcome the emerging resistance of this disease to traditional immune-chemotherapy, such as rituximab in combination with traditional chemotherapy agents. Emerging targeted therapy for relapsed refractory DLBCL encompasses more complex molecular abnormalities involving signaling pathways other than NF-κB as mechanism of resistance to immune-chemotherapy. Our review suggests that NF-κB pathway is an important crossroad where other pathways converge as phenotype of resistance that emerges in patients who fail frontline and salvage immune-chemotherapy. Future efforts should aim at targeting the role of NF-κB resistance in clinical trials, where novel agents like lenalidomide and proteasome inhibitors with established activity in this perspective will be an important component in combination therapy, along with new monoclonal antibody, BTK-inhibitors, and other novel therapy agents.

scholarly journals The Spectrum of MYC Alterations in Diffuse Large B-Cell Lymphoma

2020 ◽  
Vol 143 (6) ◽  
pp. 520-528
Author(s):  
Yang Xia ◽  
Xinlian Zhang
Keyword(s):  
B Cell ◽  
Clinical Outcomes ◽  
Copy Number ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Genetic Alterations ◽  
Gene Copy ◽  
Novel Therapy ◽  
Large B Cell Lymphoma ◽  
Large B Cell

MYC, as a powerful transcription factor, plays a vital role in various cancers. The clinical significance of MYC alterations in diffuse large B-cell lymphoma (DLBCL) has been investigated for a long time. In this study, we comprehensively summarize the different alterations of MYC in DLBCL, including MYC overexpression, <i>MYC</i> translocations, <i>MYC</i> mutations, and increased gene copy number of <i>MYC</i>. Noteworthy, lone MYC overexpression or <i>MYC</i> translocation is not significantly associated with poor clinical outcomes, and their detrimental effects depend on the genetic alterations of BCL2 or BCL6. Both double-expressor DLBCL (DE-DLBCL), defined as overexpression of MYC and BCL2 proteins, and double-hit lymphoma (DHL), defined as a dual translocation of <i>MYC</i> together with <i>BCL2</i> or <i>BCL6</i>, represent the distinct subgroups of DLBCL with inferior clinical outcomes. The mechanism may be that MYC activation induces cell proliferation, without the threat of the apoptotic brake in the presence of BCL2 overexpression. In addition, most of <i>MYC</i> mutations are present with favorable prognosis, and the nonsignificant effect of MYC copy number amplification has been observed. It has been proved that cyclophosphamide, doxorubicin, vincristine, and prednisone plus rituximab show limited effects for DHL or DE-DLBCL, and the rituximab plus dose-adjusted etoposide, prednisone, vincristine, cyclophosphamide, and doxorubicin seem to be efficacious for DHL. The novel therapy is urgently needed for clinical improvement in DHL and DE-DLBCL.

scholarly journals Splenic Micronodular T-Cell/Histiocyte-Rich Large B-Cell Lymphoma: The Corticosteroid Pretreatment Hypothesis

2021 ◽  
Author(s):  
Benzion Samueli ◽  
Karen Nalbandyan ◽  
Daniel Benharroch ◽  
Itai Levi
Keyword(s):  
T Cell ◽  
Lymph Nodes ◽  
B Cell ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Functional Changes ◽  
Major Mechanism ◽  
Large B Cell Lymphoma ◽  
Tissue Shrinkage ◽  
Large B Cell

Splenic micronodular T-cell/histiocyte-rich large B-cell lymphoma is derived from diffuse large B-cell lymphoma N.O.S., perhaps with some affinity with nodal T-cell/histiocyte-rich large B-cell lymphoma. Of note, in contrast with the latter, the only lymph nodes involved in association with the splenic micronodular pattern of the disease are the splenic hilar lymph nodes. The possibility that corticosteroids, when prescribed prior to splenectomy, cause histopathological and functional modulations, apoptosis, necrosis, tissue shrinkage, which may obscure the diagnostic morphological features of this variant lymphoma and cause and underdiagnosis of this condition. The indications for glucocorticoid therapy are either related to the lymphoma itself, or else to other comorbidities, like asthma and autoimmune disorders. We propose that patients with the splenic subset of the disease are likely to have been prescribed corticosteroids prior to histopathologic examination of the involved spleen, causing disparate morphologies. However, a reviewer might accidentally dismiss the corticosteroid pretreatment which is thus overlooked. Apoptosis, induced by corticosteroids, is hypothesized as the major mechanism initiating the histopathological and functional changes in the splenic micronodular variant of the lymphoma.

scholarly journals Evaluation of treatment patterns and survival among patients with diffuse large B-cell lymphoma in the USA

2019 ◽  
Vol 15 (9) ◽  
pp. 1021-1034 ◽  
Author(s):  
Vicki A Morrison ◽  
Yaping Shou ◽  
Jill A Bell ◽  
Laurie Hamilton ◽  
Augustina Ogbonnaya ◽  
...  
Keyword(s):  
B Cell ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Treatment Patterns ◽  
Large B Cell Lymphoma ◽  
The Usa ◽  
Large B Cell

scholarly journals Second-line rituximab–bendamustine versus rituximab–gemcitabine–oxaliplatin in diffuse large B-cell lymphoma in the real world

2019 ◽  
Vol 8 (13) ◽  
pp. 1067-1075 ◽  
Author(s):  
Raluca Ionescu-Ittu ◽  
Aijing Shang ◽  
Nancy V Velde ◽  
Annie Guerin ◽  
Yilu Lin ◽  
...  
Keyword(s):  
B Cell ◽  
Cell Lymphoma ◽  
Treatment Options ◽  
Intensive Therapy ◽  
B Cell Lymphoma ◽  
Second Line ◽  
Treatment Regimens ◽  
Large B Cell Lymphoma ◽  
The Usa ◽  
Large B Cell

Aim: Despite long-term responses to first-line immunochemotherapy, many patients with diffuse large B-cell lymphoma (DLBCL) have relapsed/refractory disease. Second-line treatment options are available. However, a large proportion of patients are ineligible for transplantation/intensive therapy. Patients & methods: This observational study of 702 patients in the USA, who used second-line therapies for relapsed/refractory DLBCL, evaluated treatment patterns and overall survival (OS). The study focused on the OS outcome of patients receiving second-line rituximab–bendamustine or rituximab–gemcitabine–oxaliplatin. Results & conclusion: Rituximab–bendamustine and rituximab–gemcitabine–oxaliplatin were received by 4.6 and 1.4% of patients, respectively (N = 42/702). Median and 1-year OS rates were similar between regimens. Many of the 200 different treatment regimens observed in second line were modified versions of National Comprehensive Cancer Network regimens.

Treatment patterns and outcomes among patients with high-intermediate/high-risk diffuse large B-cell lymphoma in the USA

Hematology ◽  
2014 ◽  
Vol 20 (8) ◽  
pp. 442-448 ◽  
Author(s):  
Daniel S. Mytelka ◽  
Li Li ◽  
Dana Stafkey-Mailey ◽  
Astra M. Liepa ◽  
Lisa M. Hess ◽  
...  
Keyword(s):  
High Risk ◽  
B Cell ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Treatment Patterns ◽  
Large B Cell Lymphoma ◽  
The Usa ◽  
Large B Cell

scholarly journals Diffuse large B cell lymphoma: using pathologic and molecular biomarkers to define subgroups for novel therapy

2014 ◽  
Vol 93 (8) ◽  
pp. 1263-1277 ◽  
Author(s):  
Antonino Carbone ◽  
Annunziata Gloghini ◽  
Yok-Lam Kwong ◽  
Anas Younes
Keyword(s):  
B Cell ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Molecular Biomarkers ◽  
Novel Therapy ◽  
Large B Cell Lymphoma ◽  
Large B Cell

scholarly journals Splenic Micronodular T-Cell/Histiocyte-Rich Large B-Cell Lymphoma: The Corticosteroid Pretreatment Hypothesis

2021 ◽  
Author(s):  
Benzion Samueli ◽  
Karen Nalbandyan ◽  
daniel benharroch ◽  
Itai Levi
Keyword(s):  
T Cell ◽  
Lymph Nodes ◽  
B Cell ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Functional Changes ◽  
Major Mechanism ◽  
Large B Cell Lymphoma ◽  
Tissue Shrinkage ◽  
Large B Cell

Splenic micronodular T-cell/histiocyte-rich large B-cell lymphoma is possibly derived from nodal T-cell/histiocyte-rich large B-cell lymphoma; however, a transition between the nodal and splenic micronodular forms has not been described to date. Of note, the only lymph nodes to be involved in association with the splenic micronodular pattern of the disease are the splenic hilar lymph nodes, and that, with partial involvement only. Kan et al, in their series of articles, have raised the possibility that corticosteroids, when prescribed prior to splenectomy, cause histopathological and functional modulations (apoptosis, necrosis, tissue shrinkage), which modify or even obscure the diagnostic morphological features. The indications for glucocorticoid therapy are either related to the suspected lymphoma, or else to other comorbidities, like asthma and autoimmune disorders. We propose that patients with the splenic, rather than nodal subset of the disease are likely to have been prescribed corticosteroids prior to histopathologic examination of the involved tissue, causing disparate morphologies in the spleen. Apoptosis, as induced by corticosteroids, is hypothesized as the major mechanism initiating the histopa-thological and functional changes in the splenic micronodular variant of our patients.

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