scholarly journals The Expression and Significance of CyclinD2, MPGES-1, Bcl2 in Diffuse Large B-cell Lymphoma

2020 ◽  
Vol 4 (6) ◽  
Author(s):  
Qiushuang Ma ◽  
Peng Lin ◽  
Bingjuan Zhou ◽  
Yafei Zhao ◽  
Ling Li ◽  
...  
Keyword(s):  
B Cell ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Tissue Type ◽  
Lymphoid Tissues ◽  
Large B Cell Lymphoma ◽  
Positive Expression ◽  
Expression Rate ◽  
The Difference ◽  
Large B Cell

Objectives: To study the expression and significance of cell cycle proteins CyclinD2, mPGES-1, Bcl2 in diffuse large B-cell lymphoma. Methods: Choose lymphoma and sexually hyperplastic lymphoid tissues as control. Immunohistochemical methods were used to detect the expression of CyclinD2, mPGES-1, and Bcl2, and to compare the positive expression rates of CyclinD2, MPGES-1 and Bcl2 in diffuse large B-cell lymphoma and reactive proliferative lymphoid tissues to compare their diffusion formation. B-cell lymphoma was analyzed for its clinicopathological features. Results: The positive expression rate of CyclinD2, mPGES-1 and Bcl2 in diffuse large B-cell lymphoma is higher than that in reactive proliferative lymphoid tissue, and the difference between the two is statistically significant. There was no statistical difference in CyclinD2, mPGES-1 and Bcl2 in diffuse large B-cell lymphoma between patients according to the age, sex, location, tissue type and degree of differentiation. Conclusion: CyclinD2, mPGES-1 and Bcl2 are highly expressed in patients with diffuse large B-cell lymphoma, and can be used as reference indicators for evaluating the malignant degree and efficacy of dysplasia.

scholarly journals A rare case of primary pulmonary diffuse large B cell lymphoma with CD5 positive expression

Open Medicine ◽  
2016 ◽  
Vol 11 (1) ◽  
pp. 49-51 ◽  
Author(s):  
Tao Wang ◽  
Mingming Zhang ◽  
Jianrong Sun ◽  
Dong Hao ◽  
Zhijiang Qi ◽  
...  
Keyword(s):  
B Cell ◽  
Clinical Symptoms ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Imaging Features ◽  
Ct Guided ◽  
Large B Cell Lymphoma ◽  
Halo Sign ◽  
Positive Expression ◽  
Large B Cell

AbstractPrimary pulmonary diffuse large B-cell lymphoma (PPDLBCL) is extremely rare. Its clinical symptoms and signs are nonspe cific, and imaging features also have not yet been well-defined. Further description is important for the diagnosis and treatment of PPDLBCL. Herein, we reported a case of a patient who suffered from bilateral chest pain and dyspnea. Computed tomography (CT) of chest demonstrated bilateral lung mass, consolidations and reverse halo sign, while consolidations and reverse halo sign are uncommon according to previous reports. Tissue samples were taken by CT guided needle biopsy. The histological samples showed PPDLBCL. This case was special in view of positive expression of CD5. After the case was treated by cyclophosphamide pirarubicin vindesine dexamethasone (CHOP) chemotherapy for six courses, her clinical symptoms were partially alleviated, while CT showed progression disease. This case report highlights different imaging features and characteristics of molecular biology, and reviews study progress of PPDLBCL.

Gene Expression Profiling of Diffuse Large B-Cell Lymphomas Supervised by CD5 Expression

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 4164-4164
Author(s):  
Kana Miyazaki ◽  
Motoko Yamaguchi ◽  
Hiroshi Imai ◽  
Satoshi Tamaru ◽  
Tohru Kobayashi ◽  
...  
Keyword(s):  
Gene Expression ◽  
B Cell ◽  
Gene Expression Profiling ◽  
Expression Profiling ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Gene Set ◽  
Large B Cell Lymphoma ◽  
The Difference ◽  
Large B Cell

Abstract Abstract 4164 Diffuse large B-cell lymphoma (DLBCL) is the most common non-Hodgkin lymphoma and is composed of heterogeneous groups of lymphoma with pathophysiological, genetic and clinical features. Gene expression profiling identified two distinct forms of DLBCL: activated B cell-like (ABC) and germinal center B-cell-like (GCB) types. ABC DLBCL shows more activated phenotype characterized with high activity of the NF-kappa B pathway and worse prognosis than GCB DLBCL. CD5-positive (CD5+) DLBCL comprises 5 to 10% of DLBCL and is one of the immunohistochemical subgroups in the 2008 WHO classification. It shows many distinct clinical characteristics with elderly onset, advanced stage at diagnosis, high serum lactate dehydrogenase level and frequent involvement of extranodal sites. Despite the use of rituximab, CD5+ DLBCL shows a poor prognosis and high incidence of central nervous system (CNS) relapse. More than 80% of patients with CD5+ DLBCL are classified as non-GCB subgroup by Hans' method; however, few molecular studies have been reported. To clarify the difference between CD5+ DLBCL and CD5-negative (CD5-) DLBCL in the gene expression profile, total RNA from 90 patients with de novo DLBCL including 33 CD5+ DLBCLs and 57 CD5- DLBCLs was examined using Agilent 44K human oligo-microarrays (Agilent 4112F). The expression of CD5 in tumor cells was confirmed by means of immunohistochemistry using frozen sections. Cases of primary mediastinal large B-cell lymphoma, intravascular large B-cell lymphoma and primary DLBCL of the CNS were excluded from the present study. Supervised hierarchical clustering of the expression data could separate the DLBCL cases into the two groups, CD5+ DLBCL and CD5- DLBCL. A signature gene set supervised by CD5 expression included some of the same genes (SH3BP5, CCND2, LMO2) in the predictor gene set to discriminate between GCB and ABC DLBCLs. To classify the difference between CD5+ ABC DLBCL and CD5- ABC DLBCL in the gene expression profile, the 90 DLBCLs were analyzed by the Rosenwald's gene set (NEJM, 2002). Those cases were separated with 78 ABC DLBCLs and 12 GCB DLBCLs. Incidence of CD5+ cases was 42% (33/78) in ABC DLBCLs and 0% in GCB DLBCLs. A classifier based on gene expression at supervised analysis also correctly identified CD5 expression in ABC DLBCL. Signature genes to distinguish between CD5+ ABC DLBCL and CD5- ABC DLBCL were as follows: SNAP25, SYCP3, CCNA1, MAPK4, CCNA1, LMO3, NLGN3, GRIN2A, AQP4, FGFR2, NEUROD1, KL, FGF1, SYT5, etc., were overexpressed in CD5+ ABC DLBCL, and CYP4Z1, MDM2, IL7R, GRLF1, TNFRSF9, CD1A etc., were overexpressed in CD5- ABC DLBCL. Enriched Gene Ontology (GO) categories in CD5+ ABC DLBCL were synapse, multicellular organismal process, fibroblast growth factor receptor signaling pathway, cell projection, alcohol dehydrogenase activity and glucuronosyltransferase activity. Among them, synapse was the top GO category (P=6.1E-05). In conclusion, our current study confirmed that most of CD5+ DLBCLs are classified as ABC DLBCL by gene expression profiling. Our results suggest that neurological component- and function-related genes in the CD5+ ABC DLBCL signature gene set may be related to the high frequency of CNS relapse in CD5+ DLBCL. Disclosures: No relevant conflicts of interest to declare.

HLA-G and MHC Class II Protein Expression in Diffuse Large B-Cell Lymphoma

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 1642-1642
Author(s):  
Dorota Jesionek-Kupnicka ◽  
Marcin Bojo ◽  
Monika Prochorec-Sobieszek ◽  
Anna Szumera-Cieckiewicz ◽  
Joanna Jablonska ◽  
...  
Keyword(s):  
Protein Expression ◽  
B Cell ◽  
Clinical Course ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Class Ii ◽  
Hla Class Ii ◽  
Large B Cell Lymphoma ◽  
Positive Expression ◽  
Large B Cell

Abstract Major histocompatibility complex (MHC) class I and class II are similar in function since they present peptides at the cell surface to CD8+ and CD4+ T cells, respectively. There is mounting evidence indicating that MHC genes play a role in the etiology and clinical course of non-Hodgkin lymphomas (NHL), especially in diffuse large B-cell lymphoma (DLBCL). We investigated the expression of human leukocyte antigen-G (HLA-G) and HLA class II protein in DLBCL among 148 patients and related their expression to the clinical course of the disease. Negative HLA-G expression was associated with a lower probability of achieving a complete remission (P= 0.04). There was no impact of HLA-G or HLA class II expression on the probability of progression-free survival (PFS). Patients with positive HLA-G expression presented a trend towards a higher 3-year overall survival (OS) rate compared to those with negative expression of HLA-G (P= 0.08). The estimated 3-year OS rate of patients with positive HLA class II expression was 59.4% (95%CI 49-69) in comparison to the 37.4% (95%CI 22-56; P= 0.04) in subjects with negative expression. In a multivariate Cox analysis adjusted for the IPI factors, we found that both the intermediate high/high IPI risk group (P= 0.001) and the loss of HLA class II expression (P= 0.05) independently increased the risk of death in the study group. We also investigated whether the impact of HLA class II expression on OS may be related to the subtypes of DLBCL. In the subgroup of 58 patients (39%) with GCB-type pattern, the patients with the loss of HLA class II expression presented a significantly lower 3-year OS rate than those with its positive expression (26% [95% CI 10-53] vs 68.2% [95% CI 51-81], P= 0.02). In contrast, in the subgroup of 90 non-GCB patients (61%), HLA class II expression did not influence OS. To further explore the unexpected favorable effect of positive HLA-G expression on the clinical course of DLBCL, we performed an additional analysis that considered the type of treatment (chemotherapy with or without rituximab). In the group of patients treated with immunochemotherapy, a more pronounced effect of the positive HLA-G expression on OS was revealed. The estimated 3-year OS rate of patients with the positive HLA-G expression was 73.3 % (95% CI 49-88) compared to 47.5% (95% CI 35-60, P= 0.03) in subjects with the negative HLA-G expression. In contrast, in the group treated with CHOP-like regimens, no significant impact of HLA-G expression on OS was observed: the 3-year OS rate for HLA-G positivity was 20% (95% CI 4-62) vs 55.3% (95% CI 37-72; P= 0.08) for the absence of HLA-G. Additionally, the prognostic value of HLA class II expression was also shown to depend on the use of rituximab as a part of first line treatment. In the patients receiving immunochemotherapy, those that had positive HLA class II expression demonstrated a 3-year OS rate of 65.3% (95% CI 52-76) compared to 29.6% (95% CI 13-53, P= 0.04) in subjects with the loss of HLA class II expression. However, HLA class II expression did not have a prognostic impact on OS in the patients treated with chemotherapy alone: the 3-year OS rate was 49.5% (95% CI 32- 67) in the subjects with positive expression in comparison to 50% (95% CI 15-85, P= 0.8) in those with the loss of HLA class II expression. In conclusion, we demonstrated for the first time expression of HLA-G protein in DLBCL and its association with the clinical course of the disease as well as we confirming the association of the loss of HLA class II protein expression with poor survival in patients treated with immunochemotherapy. Although the clinical significance of the loss of HLA class II protein expression seems to be well understood, the contribution of HLA-G to the prognosis of B-cell malignancies deserves further study, especially its immunoregulatory functions in relation to treatment with rituximab, which remains an open question. Disclosures Robak: MorphoSys AG: Research Funding.

Diffuse Large B-Cell Lymphoma—More Than a Diffuse Collection of Large B Cells: An Entity in Search of a Meaningful Classification

2009 ◽  
Vol 133 (7) ◽  
pp. 1121-1134 ◽  
Author(s):  
Sandeep Gurbaxani ◽  
John Anastasi ◽  
Elizabeth Hyjek
Keyword(s):  
B Cell ◽  
World Health Organization ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
World Health ◽  
Lymphoid Tissues ◽  
World Health Organization Classification ◽  
Large B Cell Lymphoma ◽  
Health Organization ◽  
Large B Cell

Abstract Context.—Diffuse large B-cell lymphoma is a heterogenous group of lymphomas. In this review, we present a brief description of the large number of entities recognized in the recently published (2008) World Health Organization classification of tumors of hematopoietic and lymphoid tissues. Objective.—We highlight the unique clinicopathologic and molecular genetic features of these new and previously recognized entities, to illustrate the rational for the development of this classification. To help simplify the understanding of this now large and complex group of diseases, we have attempted to create broader subgroups of related entities. We discuss large B-cell lymphoma that are not otherwise specified, those that are based on anatomic site, those that have unique histology or phenotype or genotype, those that are associated with Epstein-Barr virus or Kaposi sarcoma–associated herpesvirus and herpesvirus 8, and those that are unclassifiable. Data Sources.—World Health Organization classification of tumors of hematopoietic and lymphoid tissues (2008), published literature from PubMed (National Library of Medicine), and primary material from the authors' institution were reviewed. Conclusions.—Recognition of the different subtypes of diffuse large B-cell lymphoma as described in the World Health Organization classification scheme will lead to improved understanding of the unique clinicopathologic and genetic features associated with these subtypes of lymphoma.

BCL2 Expression Is a Prognostic Marker for the Activated B-Cell–Like Type of Diffuse Large B-Cell Lymphoma

2006 ◽  
Vol 24 (6) ◽  
pp. 961-968 ◽  
Author(s):  
Javeed Iqbal ◽  
Vishala T. Neppalli ◽  
George Wright ◽  
Bhavana J. Dave ◽  
Douglas E. Horsman ◽  
...  
Keyword(s):  
Overall Survival ◽  
B Cell ◽  
Cell Lymphoma ◽  
Mrna Level ◽  
Prognostic Significance ◽  
B Cell Lymphoma ◽  
Large B Cell Lymphoma ◽  
The Difference ◽  
Large B Cell ◽  
Bcl2 Expression

Background The role of BCL2 as a predictor of survival in diffuse large B-cell lymphoma (DLBCL) is controversial. DLBCL is heterogeneous, and the expression of BCL2 is variable within the two major subgroups of DLBCL, germinal center B-cell–like (GCB) and activated B-cell–like (ABC) DLBCL, as well as primary mediastinal DLBCL. Patients and Methods In this study, we investigated the correlation of BCL2 expression with survival in the two major subgroups of DLBCL, as well as the mechanisms of BCL2 expression. Results There was no significant correlation between BCL2 protein expression and overall survival within the GCB subgroup, but BCL2 expression had a significant adverse effect on overall survival within the ABC subgroup (P = .008). This correlation was also observed at the mRNA level (P < .04). The difference remained significant when the analyses were performed at different cutoff values. The t(14;18) was frequently observed in the GCB subgroup and was highly associated with BCL2 expression. Patients with ABC DLBCL did not exhibit t(14;18) but had a markedly higher frequency of chromosome 18q21 amplification, on which BCL2 resides. Thus, alternative mechanisms such as 18q21 amplification or activation of the nuclear factor-kappa B pathway, as reported previously, seem to be mainly responsible for the upregulation of BCL2 expression in the ABC subgroup. Conclusion Treating all DLBCL as a single entity ignores the mechanistic differences in BCL2 upregulation and obscures the prognostic significance of BCL2 expression. Hence, the significance of BCL2 and other biomarkers should be assessed in the context of DLBCL subgroups in future studies.

scholarly journals NEK2 Promotes Cell Proliferation and Glycolysis by Regulating PKM2 Abundance via Phosphorylation in Diffuse Large B-Cell Lymphoma

2021 ◽  
Vol 11 ◽  
Author(s):  
Lingna Zhou ◽  
Liya Ding ◽  
Yuqi Gong ◽  
Jing Zhao ◽  
Jing Zhang ◽  
...  
Keyword(s):  
B Cell ◽  
Cell Lymphoma ◽  
Affinity Purification ◽  
Enrichment Analysis ◽  
B Cell Lymphoma ◽  
Gene Set Enrichment Analysis ◽  
Lymphoid Tissues ◽  
Large B Cell Lymphoma ◽  
Large B Cell

Diffuse large B-cell lymphoma (DLBCL) is the most frequent and commonly diagnosed subtype of NHL, which is characterized by high heterogeneity and malignancy, and most DLBCL patients are at advanced stages. The serine/threonine kinase NEK2 (NIMA-related kinase 2), a member of NIMA-related kinase (NEK) family that regulates cell cycle, is upregulated in a variety of malignancies, including diffuse large B-cell lymphoma. However, the role and underlying mechanisms of NEK2 in DLBCL have seldom been discussed. In this study, we identified that NEK2 is upregulated in DLBCL compared to normal lymphoid tissues, and overexpression of NEK2 predicted a worse prognosis of DLBCL patients. Gene set enrichment analysis indicates that NEK2 might participate in regulating glycolysis. Knockdown of NEK2 inhibited growth and glycolysis of DLBCL cells. The interaction between NEK2 and PKM2 was discovered by tandem affinity purification and then was confirmed by immunofluorescence staining, coimmunoprecipitation, and immunoprecipitation. NEK2 bounds to PKM2 and regulates PKM2 abundance via phosphorylation, which increases PKM2 stability. The xenograft tumor model checks the influence of NEK2 on tumor growth in vivo. Thus, NEK2 could be the novel biomarker and target of DLBCL, which remarkably ameliorates the diagnosis and treatment of DLBCL.

scholarly journals Nfatc1 and Tumor Associated Macrophages Affect Progression of Certain Subsets of Diffuse Large B Cell Lymphoma Non-Gcb Subtypes

2021 ◽  
Vol 5 (2) ◽  
pp. 345-353
Author(s):  
Krisna Murti ◽  
Muslina Muslina ◽  
Ika Kartika ◽  
Rachmat Hidayat ◽  
Ella Amalia
Keyword(s):  
B Cell ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Therapeutic Strategies ◽  
Proliferation Index ◽  
Ki 67 ◽  
Large B Cell Lymphoma ◽  
Positive Expression ◽  
Activated T Cell ◽  
Large B Cell

A B S T R A C TIntroduction Diffuse large B cell lymphoma (DLBCL) is the most common type ofnon-Hodgkin lymphoma among B cell lymphomas. The interaction of tumor cellswith their microenvironment (tumor microenvironment, TME) leads to progressivityof malignancy. CD163 + macrophages known as components of TME. Nuclear factorof activated T cell (NFATc1) and MYC are important transcription factors inmalignant transformation and progression. Therapeutic strategies were fastdeveloped, nevertheless, efforts to decrease DLBCL morbidity and mortality areunsatisfied, therefore,new markers for prognosis and or therapeutic options of thepatients are necessary. This study was aimed to investigate NFATc1 expression inDLBCL and its TME. Methods: Thirty-two paraffin blocks were selected thenimmunostained for expression of NFATc1, MYC, and CD163. Clinopathologic datai.e. ages, gender, and proliferation index Ki-67 were obtained. Data was analyzedby statistics Result: Positive expression of CD163 and NFATc1 was among 55%and 45% of cases respectively. All DLBCL cases in this study were non-GCBsubtype and more patients were under 60 years (66%). Positive expression ofCD163 was higher in males (69%) and in patients under 60 years (63%). Tissuespositive for both NFATc1 and CD163 was observed higher among males andpatients under 60 years. Conclusion: NFATc1 may affect development and orprogression of certain subsets of DLBCL non-GCB subtype.

MALT lymphoma and extranodal diffuse large B-cell lymphoma are targeted by aberrant somatic hypermutation

Blood ◽  
2006 ◽  
Vol 109 (8) ◽  
pp. 3500-3504 ◽  
Author(s):  
Alexander J. A. Deutsch ◽  
Ariane Aigelsreiter ◽  
Philipp B. Staber ◽  
Alfred Beham ◽  
Werner Linkesch ◽  
...  
Keyword(s):  
B Cell ◽  
Malt Lymphoma ◽  
Cell Lymphoma ◽  
Somatic Hypermutation ◽  
Cytidine Deaminase ◽  
B Cell Lymphoma ◽  
Tissue Type ◽  
Low Grade ◽  
Large B Cell Lymphoma ◽  
Large B Cell

AbstractRecently, a novel mechanism introducing genetic instability, termed aberrant somatic hypermutation (ASHM), has been described in diffuse large B-cell lymphoma. To further investigate whether ASHM also occurs in mucosa-associated lymphoid tissue type (MALT) lymphoma, we studied the mutation profile of PIM1, PAX5, RhoH/TTF, and c-MYC in 17 MALT lymphomas and 17 extranodal diffuse large B-cell lymphomas (DLBCLs) still exhibiting a low-grade MALT lymphoma component (transformed MALT lymphoma). Mutations in one or more genes were detected in 13 (76.5%) of 17 cases of MALT lymphomas and in all of 17 (100%) cases of extranodal DLBCL. A total of 100 sequence variants were found in 30 of 34 cases, 28 in the MALT lymphomas and 72 in extranodal DLBCL. Further, in PIM1 and c-MYC some of the mutations were found to affect coding exons, leading to amino acid exchanges, thus potentially altering gene function. Expression levels of activation-induced cytidine deaminase (AID), an enzyme essential for somatic hypermutation (SHM), was associated with the mutational load. These data indicate that aberrant SHM is associated with extranodal DLBCL and MALT lymphoma, likewise. By mutating regulatory and coding sequences of the targeted genes, ASHM may represent a major contributor to their pathogenesis.

Oligoclonality of a "composite" gastric diffuse large B-cell lymphoma with areas of marginal zone B-cell lymphoma of the mucosa-associated lymphoid tissue type

2001 ◽  
Vol 440 (2) ◽  
pp. 209-214 ◽  
Author(s):  
Antonello Cabras ◽  
Gregor Weirich ◽  
Falko Fend ◽  
Jörg Nährig ◽  
Cesare Bordi ◽  
...  
Keyword(s):  
B Cell ◽  
Lymphoid Tissue ◽  
Marginal Zone ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Tissue Type ◽  
Large B Cell Lymphoma ◽  
Large B Cell
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