Gene Expression Profile of Nodal vs Extranodal Diffuse Large B-Cell Lymphoma from Saudi Arabia.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 4365-4365
Author(s):  
Zeenath Jehan ◽  
Abdul Khalid Siraj ◽  
Ronald Simon ◽  
Guido Sauter ◽  
Khawla A.l. Kuraya
Keyword(s):  
Gene Expression ◽  
Saudi Arabia ◽  
Lymph Nodes ◽  
B Cell ◽  
Expression Analysis ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Protein Translation ◽  
Large B Cell Lymphoma ◽  
Large B Cell

Abstract Diffuse large B-cell lymphoma (DLBCL) belongs to the most common malignancies in Saudi Arabia, accounting for 50–60% of adult non-Hodgkin Lymphomas. DLBCL represents a heterogeneous group of tumors with respect to morphology, genetics, and clinical behaviour. The two major subtypes of DLBCL differ in their site of origin, i.e. within (nodal) or outside (extranodal) the lymph nodes, and a separate genetic pathway has been suggested for these subtypes. To detect potential biological differences between these two DLBCL categories, we performed gene expression analysis in 20 nodal and 8 extranodal lymphoma tissues, as well as in 4 normal lymph nodes, using the GeneChip technology (Affymetrix HG-U133_2 array). Data analysis using the D chip software highlighted a total of 215 genes expression patterns of which were significantly different in nodal and extranodal lymphomas. The most striking differences were observed for genes contributing in ATP binding (20 genes), nucleotide binding (12 genes), response to stress (19 genes), RNA metabolism (6 genes), protein translation (4 genes), and inflammatory response (4 genes). Remarkably, also 5 protein tyrosine kinases were found to be differentially expressed. Our data strongly suggests the existence of at least two different genetic pathways for the development of nodal and extranodal DLBCL, which are characterized by these genetic changes. These results prompt for further expression analysis in large cohorts of histomorphologically well defined lymphoma tissues in order to evaluate the clinical relevance of these alterations.

Molecular Signature Distinguishes Between Primary Mediastinal B-Cell Lymphoma and Diffuse Large B-Cell Lymphoma with Primary Involvment of Mediastinal Lymph Nodes

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 2654-2654
Author(s):  
Jana K Mangasarova ◽  
Andrew V Misuyrin ◽  
Aminat U Magomedova ◽  
Sergey K Kravchenko
Keyword(s):  
Gene Expression ◽  
Lymph Nodes ◽  
B Cell ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Molecular Signature ◽  
Control Group ◽  
Mediastinal Lymph Nodes ◽  
Large B Cell Lymphoma ◽  
Large B Cell

Abstract Abstract 2654 Background. Primary mediastinal (thymic) B-cell lymphoma (PMBL) has been recognized as a subtype of diffuse large B-cell lymphoma (DLBCL). It has its distinctive clinical and morphological features but differs from other types of DLBCL due to peculiar immunophenotype and gene expression profile. PMBL have a distinct gene signature with several highly expressed genes including MAL, JAK2, PDL1, PDL2 and TRAF1. PMBL molecular signature was associated with a more favorable survival compared to DLBCL cases with a non-germinal and germinal-center profile, supporting a distinct natural history for PMBL [A. Rosenwald et al., 2003, G. Lenz et al., 2008]. Aim. The aim of our study was to determine whether the quantitative expression analysis of JAK2, MAL, PDL1, PDL2 and TRAF1 genes may distinguish PMBL cases from other variants of DLBCL with primary involved of mediastinal lymph nodes. Patients and methods. 31 patients with DLBCL with primary involvement of mediastinal lymph nodes and 12 patients with DLBCL without involvement of mediastinal lymph nodes were enrolled in the study. The diagnosis was made by morphological and immunophenotypic analysis of lymph nodes biopsy samples. Six healthy donors of lymphocytes constituted control group. The expression of JAK2, MAL, PDL1, PDL2 and TRAF1 genes was analyzed with RQ-PCR TaqMan hydrolyzing probes. Results. Normal median value of JAK2, MAL, PDL1, PDL2 and TRAF1 gene expression have been established according the data obtained in the set of normal donors. The gene was considered to be overexpressed if its value was more than normal median value + 3SD. In 12 patients with DLBCL without involvement of mediastinal lymph nodes there was no overexpression of MAL, PDL1 and PDL2 genes. In this group only 1 of 12 (8%) pts has the overexpression of JAK2 and 2 out of 12 (16%) pts the overexpression of TRAF1. In patients with DLBCL with primary involvement of mediastinal lymph nodes JAK2 gene was overexpressed in the 18/31 cases (58%), MAL–in the 6/31 (19%), PDL1–in the 2/31 (6%), PDL2–in the 5/31 (16%) and TRAF1–in the 2/31 (6%). Based on the overexpression of more than 3 genes we have separated from DLBCL group (31 cases) a distinct group with primary mediastinal (thymic) B-cell lymphoma 18/31 (58%) patients. So, in PMBL we revealed significant overexpression of at least 3 genes in 18/18 pts whereas in DLBCL with primary involvement of mediastinal lymph nodes no cases have such expression. Summary. Our data suggest that the quantitative molecular analysis of JAK2, MAL, PDL1, PDL2 and TRAF gene expression enables to distinguish PMBL from DLBCL with primary involvement of mediastinal lymph nodes. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Clinical quantitation of diagnostic and predictive gene expression levels in follicular and diffuse large B-cell lymphoma by RT-PCR gene expression profiling

Blood ◽  
2007 ◽  
Vol 109 (9) ◽  
pp. 3922-3928 ◽  
Author(s):  
Ebrahim Sakhinia ◽  
Caroline Glennie ◽  
Judith A. Hoyland ◽  
Lia P. Menasce ◽  
Gerard Brady ◽  
...  
Keyword(s):  
Gene Expression ◽  
Lymph Nodes ◽  
B Cell ◽  
Expression Profiling ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Cyclin B ◽  
Rt Pcr ◽  
Large B Cell Lymphoma ◽  
Large B Cell

Abstract Recent microarray gene expression profiling studies have identified gene signatures predictive of outcome, so-called “indicator” genes, for diffuse large B-cell lymphoma (DLBCL) and follicular lymphoma (FL). However, measurement of these genes in routine practice remains difficult. We applied real-time polymerase chain reaction (PCR) to polyA cDNAs prepared from 106 archived human frozen lymph nodes (63 of FL, 25 of DLBCL, 10 reactive lymph nodes, and cases with paired samples of FL [4] and subsequent DLBCL [4]). Reverse transcription and polyA reverse transcriptase (RT)–PCR was performed, and resultant cDNA was probed by real-time PCR for 36 candidate indicator genes, selected from microarray studies. Nine genes showed statistically significant different expression between FL and DLBCL, including cyclin B, COL3A1, NPM3, H731, PRKCB1, OVGL, ZFPC150, HLA-DQ-a, and XPB. Of these, cyclin B, NPM3, and COL3A1 were higher in DLBCL. Six genes showed statistically significant higher expression in the neoplastic nodes compared with reactive nodes, namely PRKCB1, BCL-6, EAR2, ZFX, cyclin B, YY1. High levels of YY.1 were associated with a shorter survival interval in both FL and DLBCL. The method is simple, sensitive, and robust, facilitating routine use and may be used as a platform for clinical measurement of prognostic gene signatures.

scholarly journals Gene expression profiling-based risk prediction and profiles of immune infiltration in diffuse large B-cell lymphoma

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Selin Merdan ◽  
Kritika Subramanian ◽  
Turgay Ayer ◽  
Johan Van Weyenbergh ◽  
Andres Chang ◽  
...  
Keyword(s):  
Gene Expression ◽  
T Cells ◽  
B Cell ◽  
Risk Prediction ◽  
Expression Profiling ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Gene Signatures ◽  
Large B Cell Lymphoma ◽  
Large B Cell

AbstractThe clinical risk stratification of diffuse large B-cell lymphoma (DLBCL) relies on the International Prognostic Index (IPI) for the identification of high-risk disease. Recent studies suggest that the immune microenvironment plays a role in treatment response prediction and survival in DLBCL. This study developed a risk prediction model and evaluated the model’s biological implications in association with the estimated profiles of immune infiltration. Gene-expression profiling of 718 patients with DLBCL was done, for which RNA sequencing data and clinical covariates were obtained from Reddy et al. (2017). Using unsupervised and supervised machine learning methods to identify survival-associated gene signatures, a multivariable model of survival was constructed. Tumor-infiltrating immune cell compositions were enumerated using CIBERSORT deconvolution analysis. A four gene-signature-based score was developed that separated patients into high- and low-risk groups. The combination of the gene-expression-based score with the IPI improved the discrimination on the validation and complete sets. The gene signatures were successfully validated with the deconvolution output. Correlating the deconvolution findings with the gene signatures and risk score, CD8+ T-cells and naïve CD4+ T-cells were associated with favorable prognosis. By analyzing the gene-expression data with a systematic approach, a risk prediction model that outperforms the existing risk assessment methods was developed and validated.

scholarly journals Targeted PET imaging strategy to differentiate malignant from inflamed lymph nodes in diffuse large B-cell lymphoma

2017 ◽  
Vol 114 (36) ◽  
pp. E7441-E7449 ◽  
Author(s):  
Jun Tang ◽  
Darin Salloum ◽  
Brandon Carney ◽  
Christian Brand ◽  
Susanne Kossatz ◽  
...  
Keyword(s):  
Lymph Nodes ◽  
B Cell ◽  
Pet Imaging ◽  
Fdg Pet ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Large B Cell Lymphoma ◽  
Imaging Approach ◽  
Imaging Strategy ◽  
Large B Cell

Diffuse large B-cell lymphoma (DLBCL) is the most common lymphoma in adults. DLBCL exhibits highly aggressive and systemic progression into multiple tissues in patients, particularly in lymph nodes. Whole-body 18F-fluodeoxyglucose positron emission tomography ([18F]FDG-PET) imaging has an essential role in diagnosing DLBCL in the clinic; however, [18F]FDG-PET often faces difficulty in differentiating malignant tissues from certain nonmalignant tissues with high glucose uptake. We have developed a PET imaging strategy for DLBCL that targets poly[ADP ribose] polymerase 1 (PARP1), the expression of which has been found to be much higher in DLBCL than in healthy tissues. In a syngeneic DLBCL mouse model, this PARP1-targeted PET imaging approach allowed us to discriminate between malignant and inflamed lymph nodes, whereas [18F]FDG-PET failed to do so. Our PARP1-targeted PET imaging approach may be an attractive addition to the current PET imaging strategy to differentiate inflammation from malignancy in DLBCL.

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