scholarly journals Prognostic significance evaluation of B-cell lymphoma 2 (BCL2) and Ki-67 expression in diffuse large B-cell lymphoma patients

2019 ◽  
Vol 6 (1) ◽  
pp. e07-e07
Author(s):  
Hossein Rahimi ◽  
Zahra Rezaei Borojerdi ◽  
Sajad Ataei Azimi ◽  
Elnaz Rashidian ◽  
Amirhossein Jafarian

Introduction: Diffuse large B-cell lymphoma (DLBCL) is the most common lymphatic neoplasm, accounting for about 30–40% of non-Hodgkin’s lymphoma cases. Objectives: DLBCL is a progressive disease with clinical, genetic and molecular heterogeneity. The prognostic value of B-cell lymphoma 2 (BCL2) and Ki-67 in DLBCL patients has been controversial. Patients and Methods: In this study, we investigated the correlation of BCL2 and Ki-67 expression with clinical features such as age, gender, B symptoms and lactate dehydrogenase (LDH) levels, subtypes of DLBCL, its staging and prognosis in 36 cases of DLBCL. The expression of BCL2 and Ki-67 was measured by immunohistochemistry. Results: There was no significant correlation between BCL2 expression and staging (P=0.082), however Ki-67 expression had a significant correlation with staging (P=0.002). There was no statistically significant correlation between BCL2 and Ki-67 with prognosis of the disease. We found a significant correlation between the germinal center B-cell (GCB) and non- GCB subtypes with BCL2 expression (P=0.024), since patients with non- GCB subtype had a higher BCL2 expression. Our study also demonstrated a significant relationship between BCL2 and Ki-67 expression, therefore, with the increase of the expression of a marker, another increases (P=0.045). Conclusion: BCL2 and Ki-67 expressions were not associated with prognosis. Overexpression of Ki-67 was associated with higher clinical stages. BCL2 expression is higher in non-GCB subtype of DLBCL. Therefore, our study shows that the subsequent studies of BCL2 and other biomarkers in the DLBCL should be based on the DLBCL subtypes.

2006 ◽  
Vol 24 (6) ◽  
pp. 961-968 ◽  
Author(s):  
Javeed Iqbal ◽  
Vishala T. Neppalli ◽  
George Wright ◽  
Bhavana J. Dave ◽  
Douglas E. Horsman ◽  
...  

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.


Blood ◽  
2005 ◽  
Vol 106 (4) ◽  
pp. 1164-1174 ◽  
Author(s):  
Jeremy S. Abramson ◽  
Margaret A. Shipp

AbstractDiffuse large B-cell lymphoma (DLBCL) displays striking heterogeneity at the clinical, genetic, and molecular levels. Clinical prognostic models can define a population at high risk for relapse following empiric chemotherapy, although such models do not account for underlying biologic differences among tumors. Commonly observed genetic abnormalities that likely contribute to pathogenesis include translocations of BCL6, BCL2, cMYC, and FAS(CD95) mutations, and aberrant somatic hypermutation. Despite recent advances in empiric chemotherapy, including interval reduction of CHOP (cyclophosphamide, doxorubicin, vincristine, prednisone) and the incorporation of anti-CD20 monoclonal antibodies, a significant proportion of patients still die of their disease. Gene expression profiling has shed light on the molecular heterogeneity within DLBCL by highlighting similarities between subsets of tumors and normal B cells, identifying features associated with unfavorable responses to empiric combination chemotherapy, and defining robust subtypes with comprehensive transcriptional signatures. Such strategies have suggested distinct routes to lymphomagenesis and have identified promising rational therapeutic targets. Additional novel therapies under investigation include those targeting BCL6 and BCL2, as well as development of novel monoclonal antibody-based therapies. Our increasing molecular understanding of the heterogeneous subsets within DLBCL will likely improve the current empiric therapy of DLBCL by identifying rational therapeutic targets in specific disease subtypes.


2020 ◽  
Author(s):  
ying duan ◽  
Yanzhen Luo ◽  
hong cen

Abstract Purpose About 30–40% of patients with diffuse large B-cell lymphoma (DLBCL) relapse or fail to respond to first-line treatment. The molecular heterogeneity is considered to be the main factor affecting the therapeutic response of DLBCL. The existing classification methods can not fully explain these heterogeneity, so we try to explain DLBCL heterogeneity by defining DLBCL subtypes from the perspective of metabolism. Methods In this study, we integrated five DLBCL data sets (GSE10846, GSE11318, GSE53786, GSE87371 and GSE23501) (n = 742) from geo database, screened 106 metabolic related genes (MAD > 0.5, Cox P < 0.001), and identified dlbcl2 subclasses (nmftype1, nmftype2) by non-negative matrix factorization clustering (NMF). Results nmftype1 showed low metabolic activity ,while nmftype2 showed high metabolic activity. Compared with the two subtypes of immune infiltration, it was found that nmftype1 was mainly infiltrated by B cells, and nmftype2 was mainly infiltrated by T cells and macrophages, and the high expression of nmftype2 was more in immune checkpoint. The difference of metabolic subtype OS was statistically significant, and the overall survival (OS) of nfmtype1 was worse than that of nmftype2. The combination of metabolic subtypes and ABCGCB subtypes can predict the prognosis of DLBCL patients better than the existing ABCGCB subtypes. Finally, 34 gene classifiers were identified. The consistency results were verified by GSE31312 (n = 470), and a new classification of DLBCL based on metabolic gene expression profile was established. Conclusions We have obtained a new DLBCL typing method, which has prognostic significance. It has a certain correlation with immune escape and can guide individualization application of immunotherapy and metabolic therapy.


2001 ◽  
Vol 18 (1) ◽  
pp. 15-22 ◽  
Author(s):  
Marta Llanos ◽  
Hugo Alvarez-Argüelles ◽  
Remedios Alemán ◽  
Juana Oramas ◽  
Lucio Díaz-Flores ◽  
...  

Author(s):  
Carla Isabelly Rodrigues‐Fernandes ◽  
Lucas Guimarães Abreu ◽  
Raghu Radhakrishnan ◽  
Danyel Elias da Cruz Perez ◽  
Gleyson Kleber Amaral‐Silva ◽  
...  

2019 ◽  
Vol 37 ◽  
pp. 353-353
Author(s):  
M. Rodriguez ◽  
I. Fernandez-Miranda ◽  
R. Mondejar ◽  
J. Capote ◽  
S. Rodriguez-Pinilla ◽  
...  

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