scholarly journals BCL-1 Gene Rearrangements in Iranian Non-Hodgkin Lymphoma Patients

2015 ◽  
Vol 8 (8) ◽  
pp. 108
Author(s):  
Manoush Tohidirad ◽  
Mehrdad Asghari Estiar ◽  
Azim Rezamand ◽  
Saeid Ghorbian ◽  
Sasan Andalib ◽  
...  
Keyword(s):  
B Cell ◽  
Cell Lymphoma ◽  
Pcr Amplification ◽  
B Cell Lymphoma ◽  
Gene Rearrangements ◽  
Non Hodgkin Lymphoma ◽  
Formalin Fixed Paraffin ◽  
Mantle Cell ◽  
Formalin Fixed Paraffin Embedded ◽  
Formalin Fixed

<p>In the present study, our aim was to assess the incidence of BCL-1 gene rearrangements in formalin-fixed paraffin embedded (FFPE) tissue in patients with non-Hodgkin lymphomas (NHL). The BIOMED-2 protocol was applied to assess the BCL-1 gene rearrangements in NHL patients. PCR amplification was carried out on FFPE in 100 patients with B-cell lymphoma including 89 cases with diffused large B-cell lymphoma (DLBCL) (15 cases under 18 years old) and 11 cases with mantle cell lymphoma (MCL). Out of the 100 patients, 19 cases (19%) were identified to have concurrent translocation involving BCL-1. The significant association was seen between BCL-1 gene rearrangements and the lymphomas in patients older than 55 years (P&lt;0.05). Out of 100 cases, 80 cases were positive and 20 cases were negative regarding CD20. No significant association was found between DLBCL lymphoma in patients under 18 years old and BCL-1 gene rearrangements (P&gt;0.05). In addition, the positive and negative expressions of LCA/CD45 marker were 76% (76/100) and 26% (26/100), respectively. Our findings revealed that BCL-1 gene rearrangement assays using BIOMED-2 protocol can be considered as a valuable approach in detection of the lymphomas.</p>

MicroRNA Profiling In Activated B-Cell and Germinal Center B-Cell Diffuse Large B-Cell Lymphoma Using Formalin Fixed, Paraffin Embedded Patient Biopsies

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 3111-3111 ◽  
Author(s):  
Betty J. Glinsmann-Gibson ◽  
Dennis E McMillan ◽  
Sarah Wilkinson ◽  
Julie Teruya-Feldstein ◽  
Lisa M. Rimsza
Keyword(s):  
B Cell ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Large B Cell Lymphoma ◽  
Formalin Fixed Paraffin ◽  
Germinal Center B Cell ◽  
Microrna Profile ◽  
Formalin Fixed Paraffin Embedded ◽  
Dlbcl Subtype ◽  
Formalin Fixed

Abstract Abstract 3111 Diffuse Large B cell lymphoma (DLBCL) is the most common form of non-Hodgkin's lymphoma. The Leukemia Lymphoma Molecular Profiling Project (LLMPP) collaboration has done extensive work regarding this disease including gene expression profiling to show that the cell of origin impacts the prognosis of the patient. Those cases which arise from an activated B cell (ABC) have a worse prognosis than those cases which arise from a germinal center B cell (GCB). We have used a subset of cases from our institution which have had gene expression profiling performed on frozen material and assigned ABC (n=18) or GCB (n=24) status (Rosenwald et al NEJM 2002, 346:1937). We have used matched formalin fixed paraffin embedded (FFPE) tissue block from these cases to obtain a microRNA profile utilizing the qNPA technology (High ThroughPut Genomics) as previously published (Roberts et al Lab Invest 2007, 87:979). This novel FFPE based RNAase protection assay measured 688 human microRNAs. Each microRNA was represented twice on the array and the values averaged for a signal value. The data were normalized to the total signal of the microarray. We were able to define a signature of increased microRNA for each DLBCL subtype as shown in Table 1. ABC subtype GCB subtype hsa-miR-155 hsa-miR-28-5p hsa-miR-196a hsa-miR-138 hsa-miR-501-3p hsa-miR-151-3p hsa-miR-656 hsa-miR-151-5p hsa-miR-1247 hsa-miR-182 hsa-miR-210 hsa-miR-613 The hsa-miR-155 is of importance in lymphoma as it regulates the generation of immunoglobulin class-switch in plasma cells (Turner et al Immunity 2007, 27:847) and was previously identified as a characteristic of ABC cell lines (Lossos et al Blood 2009,113:3754). The hsa-miR-210 has been shown to modulate the MYC antagonist MNT which allows for MYC expression (Grandori et all Cell Cycle 2009, 8:2756). This microRNA profile provides an opportunity to further explore the role microRNA plays in lymphoma biology and in particular, in DLBCL subtype determination. The success of the technique in FFPE tissue holds promise for further microRNA studies on archival material. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Molecular subtype classification of formalin-fixed, paraffin-embedded diffuse large B-cell lymphoma samples on the ICEPlex®system

2014 ◽  
Vol 167 (2) ◽  
pp. 281-285 ◽  
Author(s):  
Angela M. B. Collie ◽  
Jörk Nölling ◽  
Kiran M. Divakar ◽  
Jeffrey J. Lin ◽  
Paula Carver ◽  
...  
Keyword(s):  
B Cell ◽  
Cell Lymphoma ◽  
Molecular Subtype ◽  
B Cell Lymphoma ◽  
Large B Cell Lymphoma ◽  
Formalin Fixed Paraffin ◽  
Formalin Fixed Paraffin Embedded ◽  
Formalin Fixed ◽  
Large B Cell

PMBCL: a molecular diagnosis?

Blood ◽  
2018 ◽  
Vol 132 (22) ◽  
pp. 2319-2320 ◽  
Author(s):  
Megan S. Lim
Keyword(s):  
B Cell ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Molecular Assay ◽  
Rare Form ◽  
Large B Cell Lymphoma ◽  
Formalin Fixed Paraffin ◽  
Formalin Fixed Paraffin Embedded ◽  
Formalin Fixed ◽  
Large B Cell

In this issue of Blood, Mottok et al1 demonstrate the utility of a molecular assay that assesses the expression of 58 genes to distinguish primary mediastinal B-cell lymphoma (PMBCL) from diffuse large B-cell lymphoma (DLBCL) by using routinely available formalin-fixed paraffin-embedded tissue (FFPET) biopsies. The results could improve diagnostic accuracy for patients with PMBCL and may have important implications for clinical trial selection and interpretation of clinical outcomes for patients with this rare form of lymphoma.

scholarly journals MicroRNAs as Biomarkers of B-cell Lymphoma

2018 ◽  
Vol 13 ◽  
pp. 117727191880684 ◽  
Author(s):  
Carla Solé ◽  
Esther Arnaiz ◽  
Charles H Lawrie
Keyword(s):  
B Cell ◽  
Cell Lymphoma ◽  
Biological Fluids ◽  
B Cell Lymphoma ◽  
B Cell Development ◽  
Routine Clinical Practice ◽  
Biopsy Material ◽  
Formalin Fixed Paraffin ◽  
Formalin Fixed Paraffin Embedded ◽  
Formalin Fixed

B-cell lymphomas represent a diverse group of neoplasms classified primarily by histopatholgy and are often challenging to accurately diagnose. Despite having been recognized less than 20 years ago, microRNAs (miRNAs) have emerged as one of the most promising class of cancer molecular biomarkers and are particularly attractive as they can be readily detected in formalin-fixed paraffin-embedded biopsy material and biological fluids such as blood. Many of the identified B-cell lymphoma miRNA biomarkers also play crucial regulatory roles in normal B-cell development. Below we consider the identity, function, and biomarker potential of miRNAs in B-cell lymphoma and most importantly the barriers that remain to be overcome if they are really to become part of routine clinical practice.

Clinical Significance and Prognosis of Mir-155 and Mir-146a Expression Levels in Formalin-Fixed/Paraffin-Embedded Tissue of Patients with Diffuse Large B-Cell Lymphoma

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 5197-5197
Author(s):  
Hua Zhong
Keyword(s):  
B Cell ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Expression Levels ◽  
Large B Cell Lymphoma ◽  
Formalin Fixed Paraffin ◽  
Formalin Fixed Paraffin Embedded ◽  
Formalin Fixed ◽  
Lower Expression ◽  
Large B Cell

Abstract Abstract 5197 Introduction Diffuse large B cell lymphoma (DLBCL) is an aggressive malignancy that accounts for nearly 40% of all lymphoid tumors. Both miR-155 and miR-146a expression levels are suggested to be regulated by NF-KB expression in DLBCL. In present study, the expression of miR-155 and miR-146a were investigated to evaluate the prognosis in DLBCL patients. Patients and Methods The expression levels of miR-155 and miR-146a in formalin-fixed/paraffin-embedded tissue of patients with DLBCL (n=50) have been compared with reactive hyperplasia lymphoid nodes (n=20) by using real-time polymerase chain reaction. Clinical characters of patients such as LDH, β2-MG, International Prognostic Index (IPI), ECOG score and c-myc expression levels have also been investigated. Results 1) The expression levels of miR-155 and miR-146a were significantly higher in DLBCL patients than control (P<0.001). (Fig 1) 2) The expression levels of miR-155 and miR-146a were different between germinal center B-cell like DLBCL (GCB-DLBCL) and activated B-cell-like DLBCL (ABC-DLBCL), but the difference had no significance (P>0.05). 3) There was correlation between the expression of miR-155 and miR-146a in DLBCL patients (r =0.639, P<0.001). 4) There was positive correlation in the expression of miR-146a with LDH, β2-MG, IPI, ECOG score and c-myc expression levels in DLBCL patients. 5) Lower expression levels of miR-155 and miR-146a were found to be associated with high complete remission (CR) rate and overall response (OR) rate in DLBCL patients (P<0.05). 6) Lower expression levels of miR-146a in DLBCL patients were only associated with better 5 years progression free survival (5y-PFS) (P=0.044), but lower expression levels of miR-155 in DLBCL patients were associated with better 5y-PFS (P=0.013) and 5 years overall survival (5y-OS) (P=0.007). 7) Multivariate analysis using a Cox proportional hazard model confirmed that either miR-155 or miR-146a was the independent predictor. (For miR-155 5y-PFS, Hazards ratio 0.260, 95% CI, 0.058–0.801; for miR-146a 5y-PFS, Hazards ratio 0.251, 95% CI, 0.068–0.922) 8) Compared to CHOP protocol, the higher miR-155 expression level patients who chose R-CHOP protocol for treatment achieved better 3y-PFS and 3y-OS (P<0.05). Conclusions The expression levels of miR-155 and miR-146a were higher in DLBCL patients. Moreover, high expressions of these two microRNAs were associated with the disease progression. Patients with higher miR-155 expression levels may be benefit from the protocol including Rituximab. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Splenic B-Cell Lymphoma/Leukemia, Unclassifiable in Japan

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 5301-5301
Author(s):  
Takaharu Suzuki ◽  
Hiroaki Miyoshi ◽  
Keisuke Kawamoto ◽  
Joji Shimono ◽  
Jun Takizawa ◽  
...  
Keyword(s):  
B Cell ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Cyclin D3 ◽  
Hairy Cell ◽  
Cell Leukemia ◽  
Braf Mutations ◽  
Formalin Fixed Paraffin ◽  
Formalin Fixed Paraffin Embedded ◽  
Formalin Fixed

Abstract Introduction Splenic B-cell lymphoma/leukemia, unclassifiable is defined as being unable to be classified as any other B-cell neoplasm infiltrating the spleen (World Health Organization Classification of Tumors of Haematopoietic and Lymphoid Tissue 2017). In splenic B-cell lymphoma/leukemia, unclassifiable, splenic diffuse red pulp small cell lymphoma (SDRPL) and hairy cell leukemia variant (HCL-v) are provisionally defined. The incidence of these diseases is rare. It has been reported that they account for 9% of splenic B-cell lymphomas (Haematologica 2010;95:1122-1129). There are no reports of histopathological examinations or BRAF mutations (V600E) in Japan. It has been shown that BRAF mutations (V600E) are found in all patients with Hairy cell leukemia-classical (HCL-c) (N Engl J Med. 2011 364: 2305-2315). This study aimed to clarify the pathological features of splenic B-cell lymphoma/leukemia, unclassifiable. Methods We analyzed 5 cases of suspected splenic B-cell lymphoma/leukemia, unclassifiable in terms of splenectomy. Five cases include 0 cases of SDRPL, 2 cases of HCL-v, and 3 cases of splenic B-cell lymphoma/leukemia, unclassifiable not applicable to either case. We analyzed patients undergoing splenectomy who were pathologically diagnosed at the Kurume University Pathology Course between July 2012 and May 2017. Splenic B-cell lymphoma/leukemia, unclassifiable was suspected in 5 cases. From the findings of peripheral blood, bone marrow, and BRAF mutation (V600E) analyses, 2 patients were diagnosed with HCL-v. The other 3 patients were diagnosed with splenic B-cell lymphoma/leukemia, unclassifiable. Pathological examinations were performed in these cases. Marker expression analysis of the B-cell line was performed using immunohistochemical (IHC) staining and flow cytometry (FCM). IHC staining was performed on formalin-fixed paraffin-embedded samples. For FCM analysis, we confirmed the clonality of B cells and analyzed their expression. A positive judgment was made at 30% or greater. For BRAF mutation (V600E) analysis, deoxyribonucleic acid was extracted from formalin-fixed paraffin-embedded samples and performed using the Sanger sequencing method. Results The results of the analysis are shown in Table 1. HCL-v cases included 1 man and 1 woman, and the age was 62-71 years old. Splenic B-cell lymphoma/leukemia, unclassifiable cases included 2 men and 1 woman, and the age was 56-66 years. Splenic B-cell lymphoma/leukemia, unclassifiable cases involved bone marrow infiltration of B-cell lymphoma in 2 cases. In 3 cases of splenic B-cell lymphoma/leukemia, unclassifiable, there were no cases in which hairy cells were recognized in the peripheral blood. In all cases of splenic B-cell lymphoma/leukemia, unclassifiable, BRAF mutations (V600E) were not observed. All cases of splenic B-cell lymphoma/leukemia, unclassifiable and HCL-v tested positive for cluster of differentiation (CD)20, CD19, and B-cell lymphoma (Bcl-2) and tested negative for CD103 and CD10. All HCL-v cases and 2 of 3 cases of splenic B-cell lymphoma/leukemia, unclassifiable tested positive for cyclin D3. One case of splenic B-cell lymphoma/leukemia, unclassifiable tested positive for CD5, but negative for lymphoid enhancer-binding factor 1 (LEF1), cyclin D1, and Sox11. All other cases tested negative for CD5, LEF1, cyclin D1, and Sox11. One of two cases of HCL-v and 2 of 3 cases of splenic B-cell lymphoma/leukemia, unclassifiable tested positive for CD11c. All HCL-v cases tested negative and 1 of 3 cases of splenic B-cell lymphoma/leukemia, unclassifiable tested positive for Bcl-6. IHC staining was performed because FCM was not performed in 1 case of HCL-v. There was no obvious bias in κ and λ. One patient with HCL-v who underwent FCM was κ-positive. Splenic B-cell lymphoma/leukemia, unclassifiable was κ-positive in all cases. Conclusions In this analysis, splenic B-cell lymphoma/leukemia, unclassifiable did not involve BRAF mutations (V600E) in all cases. It has been reported that cyclin D3 is highly expressed in SDRPL. Splenic B-cell lymphoma/leukemia, unclassifiable and HCL-v confirmed the same tendency (Blood. 2017; 129:1042-1045). Further molecular biological analysis for splenic B-cell lymphoma/leukemia, unclassifiable is desired. Disclosures No relevant conflicts of interest to declare.

scholarly journals Molecular Classification of Small B-Cell Lymphomas Using Digital Multiplexed Gene Expression Applicable to Formalin-Fixed Paraffin-Embedded Tissues

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 5770-5770
Author(s):  
Min Xiao ◽  
Jianfeng Zhou ◽  
Wei Zhang
Keyword(s):  
B Cell ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Molecular Classification ◽  
Classification Model ◽  
B Cell Lymphomas ◽  
Formalin Fixed Paraffin ◽  
Mantle Cell ◽  
Formalin Fixed Paraffin Embedded

Background: Small B-cell lymphomas encompass a group of lymphoid neoplasms with high heterogeneity. However, the lack of relatively specific diagnostic markers for most of these diseases make their diagnosis challenging. Methods: Using NanoString platform, a random forest-based molecular classification model was trained on 203 malignant and 98 non-malignant formalin-fixed paraffin-embedded (FFPE) tissues. Candidate genes were selected from microarray gene expression data of 891 small B-cell lymphomas. All malignant biopsies were derived from individuals diagnosed as a well-defined small B-cell lymphoma entity, including 17 chronic lymphocytic leukemia/small lymphocytic B-cell lymphoma (CLL/SLL), 74 follicular lymphoma (FL), 34 classical mantle cell lymphoma (cMCL), 5 non-nodal mantle cell lymphoma (nnMCL), 56 mucosa-associated lymphoid tissue lymphoma (MALT), 3 splenic marginal zone lymphoma (SMZL), and 14 nodal marginal zone lymphoma (NMZL). A leave-one-out prediction (CLL/SLL, FL, MCL, MZL, and non-malignancy) was applied to test the accuracy of prediction of the model, and Gini Index of each gene was taken into consideration in simplifying the molecular assay applicable to routine test. Results: A total of 154 candidate genes were initially selected for training the molecular classification model. Genes were initially selected for training the molecular classification model. Thirty-two genes were specifically highly expressed in a single subgroup with Gini Index more than 0.001. The most important genes for classification were CCND1, ZBTB32, MME, BHLHE41, SOX11, and RGS13. The most distinguishable entity was CLL/SLL (ZBTB32, CLNK, and CD200), followed by cMCL/nnMCL (CCND1 and SOX11), and FL (MME, RGS13, and ELL3). Using the molecular classification model trained on the most specific 33 genes, the consistency of diagnosis were 97.5%. Conclusions: In conclusion, our molecular model robustly recognized different subtypes of small B-cell lymphomas in leukemic FFPE samples, which provides a novel approach to precise diagnosis and classification of small B-cell lymphomas. Figure Disclosures Zhou: Nanjing Iaso Biotherapeutics Co. Ltd.: Other: Chairman of Advisory Committee of Science and Medicine.

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