Molecular Signatures Define New Rational Treatment Targets in Large B-Cell Lymphomas

Hematology ◽  
2007 ◽  
Vol 2007 (1) ◽  
pp. 265-269 ◽  
Author(s):  
Margaret A. Shipp
Keyword(s):  
B Cell ◽  
Clinical Investigation ◽  
Expression Profiles ◽  
Gene Expression Profiles ◽  
Molecular Signatures ◽  
B Cell Lymphomas ◽  
Treatment Regimens ◽  
Lymphoid Malignancies ◽  
Survival Pathways ◽  
Large B Cell

Abstract Diffuse large B-cell lymphomas (DLBCLs), the most common lymphoid malignancies, are clinically and genetically heterogeneous disorders. Although DLBCL is a chemo-responsive tumor, many patients will not be cured with conventional empiric treatment regimens. Gene expression profiles, analyses of specific genetic abnormalities and functional assays have been used to develop comprehensive molecular signatures of tumors that share similar features and rely upon common survival pathways. These studies are leading to the identification of subtype-specific rational therapeutic targets and associated inhibitors for clinical investigation.

scholarly journals Prognostic Significance of in situ Phenotypic Marker Expression in Diffuse Large B-cell Lymphomas

2007 ◽  
Vol 2 ◽  
pp. 117727190700200 ◽  
Author(s):  
Alexandar Tzankov ◽  
Philip Went ◽  
Stephan Dirnhofer
Keyword(s):  
B Cell ◽  
Expression Profiles ◽  
Prognostic Significance ◽  
Gene Expression Profiles ◽  
Small Sample ◽  
B Cell Lymphomas ◽  
Phenotypic Marker ◽  
Small Sample Sizes ◽  
Protein Expression Profiles ◽  
Large B Cell

Diffuse large B-cell lymphomas (DLBCL) are the most common lymphoid malignancies, and encompass all malignant lymphomas characterized by large neoplastic cells and B-cell derivation. In the last decade, DLBCL has been subjected to intense clinical, phenotypic and molecular studies, and were found to represent a heterogeneous group of tumors. These studies suggested new disease subtypes and variants with distinct clinical characteristics, morphologies, immunophenotypes, genotypes or gene expression profiles, associated with distinct prognoses or unique sensitivities to particular therapy regimens. Unfortunately, the reliability and reproducibility of the molecular results remains unclear due to contradictory reports in the literature resulting from small sample sizes, referral and selection biases, and variable methodologies and cut-off levels used to determine positivity. Here, we review phenotypic studies on the prognostic significance of protein expression profiles in DLBCL and reconsider our own retrospective data on 301 primary DLBCL cases obtained on a previously validated tissue microarray in light of powerful statistical methods of determining optimal cut-off values of phenotypic factors for prediction of outcome.

Distinct Gene Expression Profiles: Nodal versus Extranodal Diffuse Large B-Cell Lymphoma

Oncology ◽  
2008 ◽  
Vol 75 (1-2) ◽  
pp. 71-80 ◽  
Author(s):  
Zeenath Jehan ◽  
Abdul K. Siraj ◽  
Jehad Abubaker ◽  
Christian Ruiz ◽  
Ronald Simon ◽  
...  
Keyword(s):  
Gene Expression ◽  
B Cell ◽  
Cell Lymphoma ◽  
Expression Profiles ◽  
Gene Expression Profiles ◽  
B Cell Lymphoma ◽  
Distinct Gene ◽  
Large B Cell Lymphoma ◽  
Large B Cell

scholarly journals SYK Inhibition Modulates Distinct PI3K/AKT- Dependent Survival Pathways and Cholesterol Biosynthesis in Diffuse Large B Cell Lymphomas

Cancer Cell ◽  
2013 ◽  
Vol 23 (6) ◽  
pp. 826-838 ◽  
Author(s):  
Linfeng Chen ◽  
Stefano Monti ◽  
Przemyslaw Juszczynski ◽  
Jing Ouyang ◽  
Bjoern Chapuy ◽  
...  
Keyword(s):  
B Cell ◽  
Cholesterol Biosynthesis ◽  
B Cell Lymphomas ◽  
Survival Pathways ◽  
Large B Cell

Nodal marginal zone lymphoma: gene expression and miRNA profiling identify diagnostic markers and potential therapeutic targets

Blood ◽  
2012 ◽  
Vol 119 (3) ◽  
pp. e9-e21 ◽  
Author(s):  
Alberto J. Arribas ◽  
Yolanda Campos-Martín ◽  
Cristina Gómez-Abad ◽  
Patrocinio Algara ◽  
Margarita Sánchez-Beato ◽  
...  
Keyword(s):  
Gene Expression ◽  
B Cell ◽  
Marginal Zone ◽  
Expression Profiles ◽  
Gene Expression Profiles ◽  
Marginal Zone Lymphoma ◽  
Survival Pathways ◽  
Gene Sets ◽  
Nodal Marginal Zone Lymphoma ◽  
Follicular Lymphomas

Abstract Nodal marginal zone lymphoma (NMZL) is a small B-cell neoplasm whose molecular pathogenesis is still essentially unknown and whose differentiation from other small B-cell lymphomas is hampered by the lack of specific markers. We have analyzed gene expression, miRNA profile, and copy number data from 15 NMZL cases. For comparison, 16 follicular lymphomas (FLs), 9 extranodal marginal zone lymphomas, and 8 reactive lymph nodes and B-cell subtypes were included. The results were validated by quantitative RT-PCR in an independent series, including 61 paraffin-embedded NMZLs. NMZL signature showed an enriched expression of gene sets identifying interleukins, integrins, CD40, PI3K, NF-κB, and TGF-β, and included genes expressed by normal marginal zone cells and memory B cells. The most highly overexpressed genes were SYK, TACI, CD74, CD82, and CDC42EP5. Genes linked to G2/M and germinal center were down-regulated. Comparison of the gene expression profiles of NMZL and FL showed enriched expression of CHIT1, TGFB1, and TACI in NMZL, and BCL6, LMO2, and CD10 in FL. NMZL displayed increased expression of miR-221, miR-223, and let-7f, whereas FL strongly expressed miR-494. Our study identifies new candidate diagnostic molecules for NMZL and reveals survival pathways activated in NMZL.

scholarly journals Mechanisms of resistance to EZH2 inhibitors in diffuse large B-cell lymphomas

Blood ◽  
2018 ◽  
Vol 131 (19) ◽  
pp. 2125-2137 ◽  
Author(s):  
Malik Bisserier ◽  
Narendra Wajapeyee
Keyword(s):  
B Cell ◽  
Resistance Mechanisms ◽  
Drug Binding ◽  
Mechanisms Of Resistance ◽  
B Cell Lymphomas ◽  
Survival Pathways ◽  
Key Points ◽  
Large B Cell

Key Points Resistance to EZH2 inhibitors occurs due to the activation of survival pathways and acquired EZH2 mutations that prevent drug binding. Resistance mechanisms for different EZH2 inhibitors varies. Thus, cells resistant to 1 EZH2 inhibitor are sensitive to other inhibitors.

Expression of the BAFF-R (BR3) Is Positive in a Minority of Diffuse Large B Cell Lymphomas and Does Not Correlate with the Germinal Center or Non Germinal Center Origin of Lymphomatous Cells.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 4711-4711
Author(s):  
Alexis Proust ◽  
Idir Adrar ◽  
Patricia Rince ◽  
Virginie Mercier ◽  
Thierry Lazure ◽  
...  
Keyword(s):  
B Cells ◽  
B Cell ◽  
Germinal Center ◽  
Expression Profiles ◽  
Statistical Significance ◽  
Lymphocytic Leukemia ◽  
Response To Treatment ◽  
Specific Receptor ◽  
B Cell Lymphomas ◽  
Large B Cell

Abstract BAFF, a member of the TNF family, has been shown to be implicated in B cell maturation and survival through an interaction with its three receptors, BCMA, TACI and BAFF-R. Recent data revealed that it also plays a role in B cell malignancies. For exemple, an autocrine activation of the BAFF receptors could participate to oncogenesis during multiple myeloma or chronic lymphocytic leukemia. BAFF-R, the sole BAFF specific receptor, is expressed in a subset of Diffuse Large B Cell Lymphomas (DLBCL). Since BAFF-R activation in B cells leads to cell proliferation and survival, expression of this receptor in DLBCL could correlate with more aggressive lymphomas. DLBCL can be divided into prognostically important subgroups with germinal center B cell-like (GCB), activated B cell-like (ABC) and type 3 gene expression profiles using a cDNA microarray. The germinal center origin of malignant B cells in DLBCL can also be characterized by immunohistochemistry (IHC) according to CD10, Bcl6 CD138 and MUM1 expression. In this work, we investigated whether expression of BAFF-R in DLBCL correlate or not with the GCB vs non GCB phenotype of lymphomatous cells. Lymph nodes biopsies from 23 DLBCL (among whom 3 post-transplantation lymphomas and 1 AIDS-related DLBCL) were analyzed. In a first step, we characterized by IHC the precise phenotype of each DLBCL: CD10+/Bcl6+ DLBCL were classified into the germinal center (GCB) group (n=9), whereas CD10-/BCL6-/MUM1+ lymphomas defined the non germinal center (NGCB) one (n=14). Each DLBCL was then analyzed for BAFF-R expression by IHC. In agreement with a recent report, most of the DLBCL were found to be negative for BAFF-R expression (16 out of 23). Interestingly, 4 of the 9 GCB DLBCL were found to be BAFF-R positive (44%), whereas only 3 out of 14 (21%) in the NGCB group. Although the difference did not reach statistical significance, we concluded from this observation that a consequent percentage of GCB DLBCL express the specific receptor BAFF-R. Thus, we actually analyze the clinical and biological characteristics of BAFF-R positive DLBCL and investigate whether expression of BAFF-R could represent a bad prognosis factor in term of clinical outcome and response to treatment.

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