scholarly journals BCL2 Overexpression Associated With Chromosomal Amplification in Diffuse Large B-Cell Lymphoma

Blood ◽  
1997 ◽  
Vol 90 (3) ◽  
pp. 1168-1174 ◽  
Author(s):  
Outi Monni ◽  
Heikki Joensuu ◽  
Kaarle Franssila ◽  
Juha Klefstrom ◽  
Kari Alitalo ◽  
...  
Keyword(s):  
B Cell ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Comparative Genomic ◽  
Chain Gene ◽  
Large B Cell Lymphoma ◽  
Bcl2 Protein ◽  
High Level ◽  
Hodgkin's Lymphomas ◽  
Large B Cell

Abstract Gene activation by translocation between an oncogene and an immunoglobulin heavy-chain gene, which leads to increased expression of the oncoprotein, is a well-known mechanism in the genesis of B-cell lymphomas. In contrast, the role of gene amplification in activation of oncogenes in non-Hodgkin's lymphomas is poorly characterized. To study the BCL2 amplification we performed comparative genomic hybridization (CGH), Southern blot hybridization, Western analysis, immunohistochemistry, metaphase fluorescence in situ hybridization, and chromosome analysis on 26 cases of diffuse large B-cell lymphoma (large noncleaved cell lymphoma). The gain or high-level amplification of 18q was found in eight tumors (31%) by CGH, and Southern analysis revealed BCL2 amplification in these cases, but not in the cases with normal chromosome 18 or t(14; 18)(q32; q21). Western immunoblot analysis and immunohistochemistry revealed a high-level expression of BCL2 protein in the cases with BCL2 amplification and t(14; 18)(q32; q21). However, translocation (14; 18)(q32; q21) was not detected in any of the cases with BCL2 amplification. Therefore, our results suggest that amplification of the BCL2 gene is an important mechanism for BCL2 protein overexpression in diffuse large B-cell lymphoma.

scholarly journals BCL2 Overexpression Associated With Chromosomal Amplification in Diffuse Large B-Cell Lymphoma

Blood ◽  
1997 ◽  
Vol 90 (3) ◽  
pp. 1168-1174 ◽  
Author(s):  
Outi Monni ◽  
Heikki Joensuu ◽  
Kaarle Franssila ◽  
Juha Klefstrom ◽  
Kari Alitalo ◽  
...  
Keyword(s):  
B Cell ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Comparative Genomic ◽  
Chain Gene ◽  
Large B Cell Lymphoma ◽  
Bcl2 Protein ◽  
High Level ◽  
Hodgkin's Lymphomas ◽  
Large B Cell

Gene activation by translocation between an oncogene and an immunoglobulin heavy-chain gene, which leads to increased expression of the oncoprotein, is a well-known mechanism in the genesis of B-cell lymphomas. In contrast, the role of gene amplification in activation of oncogenes in non-Hodgkin's lymphomas is poorly characterized. To study the BCL2 amplification we performed comparative genomic hybridization (CGH), Southern blot hybridization, Western analysis, immunohistochemistry, metaphase fluorescence in situ hybridization, and chromosome analysis on 26 cases of diffuse large B-cell lymphoma (large noncleaved cell lymphoma). The gain or high-level amplification of 18q was found in eight tumors (31%) by CGH, and Southern analysis revealed BCL2 amplification in these cases, but not in the cases with normal chromosome 18 or t(14; 18)(q32; q21). Western immunoblot analysis and immunohistochemistry revealed a high-level expression of BCL2 protein in the cases with BCL2 amplification and t(14; 18)(q32; q21). However, translocation (14; 18)(q32; q21) was not detected in any of the cases with BCL2 amplification. Therefore, our results suggest that amplification of the BCL2 gene is an important mechanism for BCL2 protein overexpression in diffuse large B-cell lymphoma.

Array-Based Comparative Genomic Hybridization Analysis Reveals Recurrent Chromosomal Alterations and Prognostic Parameters in Primary Cutaneous Large B-Cell Lymphoma

2006 ◽  
Vol 24 (2) ◽  
pp. 296-305 ◽  
Author(s):  
Remco Dijkman ◽  
Cornelis P. Tensen ◽  
Ekaterina S. Jordanova ◽  
Jeroen Knijnenburg ◽  
Juliette J. Hoefnagel ◽  
...  
Keyword(s):  
B Cell ◽  
Comparative Genomic Hybridization ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Comparative Genomic ◽  
Genomic Hybridization ◽  
Chromosomal Alterations ◽  
Large B Cell Lymphoma ◽  
High Level ◽  
Large B Cell

Purpose To evaluate the clinical relevance of genomic aberrations in primary cutaneous large B-cell lymphoma (PCLBCL). Patients and Methods Skin biopsy samples of 31 patients with a PCLBCL classified as either primary cutaneous follicle center lymphoma (PCFCL; n = 19) or PCLBCL, leg type (n = 12), according to the WHO–European Organisation for Research and Treatment of Cancer (EORTC) classification, were investigated using array-based comparative genomic hybridization, fluorescence in situ hybridization (FISH), and examination of promoter hypermethylation. Results The most recurrent alterations in PCFCL were high-level DNA amplifications at 2p16.1 (63%) and deletion of chromosome 14q32.33 (68%). FISH analysis confirmed c-REL amplification in patients with gains at 2p16.1. In PCLBCL, leg type, most prominent aberrations were a high-level DNA amplification of 18q21.31-q21.33 (67%), including the BCL-2 and MALT1 genes as confirmed by FISH, and deletions of a small region within 9p21.3 containing the CDKN2A, CDKN2B, and NSG-x genes. Homozygous deletion of 9p21.3 was detected in five of 12 patients with PCLBCL, leg type, but in zero of 19 patients with PCFCL. Complete methylation of the promoter region of the CDKN2A gene was demonstrated in one PCLBCL, leg type, patient with hemizygous deletion, in one patient without deletion, but in zero of 19 patients with PCFCL. Seven of seven PCLBCL, leg type, patients with deletion of 9p21.3 and/or complete methylation of CDKN2A died as a result of their lymphoma. Conclusion Our results demonstrate prominent differences in chromosomal alterations between PCFCL and PCLBCL, leg type, that support their classification as separate entities within the WHO-EORTC scheme. Inactivation of CDKN2A by either deletion or methylation of its promoter could be an important prognostic parameter for the group of PCLBCL, leg type.

Primary Mediastinal (Thymic) Large B-Cell Lymphoma: A Short Review With Brief Discussion of Mediastinal Gray Zone Lymphoma

2011 ◽  
Vol 135 (3) ◽  
pp. 394-398 ◽  
Author(s):  
Charles Blake Hutchinson ◽  
Endi Wang
Keyword(s):  
B Cell ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Short Review ◽  
Comparative Genomic ◽  
Gray Zone ◽  
Superior Mediastinum ◽  
Gray Zone Lymphoma ◽  
Large B Cell Lymphoma ◽  
Large B Cell

Abstract Primary mediastinal (thymic) large B-cell lymphoma (PMBCL) is a subtype of diffuse large B-cell lymphoma (DLBCL). It commonly presents as a bulky lesion in the anterior-superior mediastinum with symptoms related to local invasion or compression. Microscopic examination typically shows infiltration of medium-large cells surrounded by collagen fibrosis. The neoplastic cells express B-cell markers, and CD30 often shows heterogeneous staining. Comparative genomic hybridization has identified gains in loci of 9p24 and 2p15 as well as Xp11.4-21 and Xq24-26. Amplification of REL and BCL11A at 2p as well as elevated expression of JAK2, PDL1, and PDL2 at 9p has been demonstrated. Nodular sclerosis classic Hodgkin lymphoma needs to be differentiated from PMBCL and cases with overlapped features have been described as mediastinal gray zone lymphoma. Primary mediastinal (thymic) large B-cell lymphoma carries a favorable prognosis in comparison to conventional DLBCL.

scholarly journals Concurrent Expression of MYC and BCL2 in Diffuse Large B-Cell Lymphoma Treated With Rituximab Plus Cyclophosphamide, Doxorubicin, Vincristine, and Prednisone

2012 ◽  
Vol 30 (28) ◽  
pp. 3452-3459 ◽  
Author(s):  
Nathalie A. Johnson ◽  
Graham W. Slack ◽  
Kerry J. Savage ◽  
Joseph M. Connors ◽  
Susana Ben-Neriah ◽  
...  
Keyword(s):  
Protein Expression ◽  
B Cell ◽  
Cell Lymphoma ◽  
Molecular Subtype ◽  
International Prognostic Index ◽  
Prognostic Index ◽  
B Cell Lymphoma ◽  
Large B Cell Lymphoma ◽  
Bcl2 Protein ◽  
Large B Cell

Purpose Diffuse large B-cell lymphoma (DLBCL) is curable in 60% of patients treated with rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP). MYC translocations, with or without BCL2 translocations, have been associated with inferior survival in DLBCL. We investigated whether expression of MYC protein, with or without BCL2 protein expression, could risk-stratify patients at diagnosis. Patients and Methods We determined the correlation between presence of MYC and BCL2 proteins by immunohistochemistry (IHC) with survival in two independent cohorts of patients with DLBCL treated with R-CHOP. We further determined if MYC protein expression correlated with high MYC mRNA and/or presence of MYC translocation. Results In the training cohort (n = 167), MYC and BCL2 proteins were detected in 29% and 44% of patients, respectively. Concurrent expression (MYC positive/BCL2 positive) was present in 21% of patients. MYC protein correlated with presence of high MYC mRNA and MYC translocation (both P < .001), but the latter was less frequent (both 11%). MYC protein expression was only associated with inferior overall and progression-free survival when BCL2 protein was coexpressed (P < .001). Importantly, the poor prognostic effect of MYC positive/BCL2 positive was validated in an independent cohort of 140 patients with DLBCL and remained significant (P < .05) after adjusting for presence of high-risk features in a multivariable model that included elevated international prognostic index score, activated B-cell molecular subtype, and presence of concurrent MYC and BCL2 translocations. Conclusion Assessment of MYC and BCL2 expression by IHC represents a robust, rapid, and inexpensive approach to risk-stratify patients with DLBCL at diagnosis.

scholarly journals One Patient, Two Uncommon B-Cell Neoplasms: Solitary Plasmacytoma following Complete Remission from Intravascular Large B-Cell Lymphoma Involving Central Nervous System

2014 ◽  
Vol 2014 ◽  
pp. 1-6 ◽  
Author(s):  
Joycelyn Lee ◽  
Soo Yong Tan ◽  
Leonard H. C. Tan ◽  
Hwei Yee Lee ◽  
Khoon Leong Chuah ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
B Cell ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Solitary Plasmacytoma ◽  
B Cell Malignancies ◽  
Large B Cell Lymphoma ◽  
Hodgkin's Lymphomas ◽  
Large B Cell

Second lymphoid neoplasms are an uncommon but recognized feature of non-Hodgkin’s lymphomas, putatively arising secondary to common genetic or environmental risk factors. Previous limited evaluations of clonal relatedness between successive mature B-cell malignancies have yielded mixed results. We describe the case of a man with intravascular large B-cell lymphoma involving the central nervous system who went into clinical remission following immunochemotherapy and brain radiation, only to relapse 2 years later with a plasmacytoma of bone causing cauda equina syndrome. The plasmacytoma stained strongly for the cell cycle regulator cyclin D1 on immunohistochemistry, while the original intravascular large cell lymphoma was negative, a disparity providing no support for clonal identity between the 2 neoplasms. Continued efforts atcataloging and evaluating unique associations of B-cell malignancies are critical to improving understanding of overarching disease biology in B-cell malignancies.

scholarly journals Chromosomal Imbalances in Diffuse Large B-Cell Lymphoma Detected by Comparative Genomic Hybridization

2002 ◽  
Vol 15 (8) ◽  
pp. 807-816 ◽  
Author(s):  
Mattias Berglund ◽  
Gunilla Enblad ◽  
Emma Flordal ◽  
Weng-Onn Lui ◽  
Carin Backlin ◽  
...  
Keyword(s):  
B Cell ◽  
Comparative Genomic Hybridization ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Comparative Genomic ◽  
Genomic Hybridization ◽  
Chromosomal Imbalances ◽  
Large B Cell Lymphoma ◽  
Large B Cell
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