Effect of CD20 Expression Levels On B-Cell Lymphoma Patients' Background and Prognosis.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 5000-5000
Author(s):  
Yuhko Suzuki ◽  
Tsutomu Yoshida ◽  
Naoya Nakamura ◽  
Tomiteru Togano ◽  
Koji Miyazaki ◽  
...  
Keyword(s):  
Flow Cytometry ◽  
Overall Survival ◽  
B Cell ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
World Health ◽  
Expression Levels ◽  
Significant Difference ◽  
Cd20 Expression ◽  
Anti Cd20

Abstract Abstract 5000 AIM The anti-CD20 antibody Rituximab has improved the disease-free survival and overall survival of patients with several types of B-cell lymphoma, in which CD20 is expressed on the cell surface and in the cytoplasm. Flow cytometry indicated that CD20 expression varies from null, weak to strong. Despite its clinical importance, the influence of CD20 expression levels on lymphoma therapy has not been well elucidated. Patients, Material and Methods 214 cases were analyzed, all newly diagnosed with B-cell lymphoma at our institute from January in 2002 to April in 2009. All were biopsied and analyzed by flow cytometry. The biopsy specimens were fixed in formalin and stained with Hematoxylin-Eosin; they were also immunostained. Histological subtypes were defined according to the World Health Organization Classification Ver. 3. The mean florescence intensities of CD20 and CD19 were determined by flow cytometry, and cytoplasmic expression of CD20 was determined by immunohistochemistry. 1) The cases were categorized as follows: A: CD20-negative, B: CD20/19 less than 20%, C: CD20/19 20-50% and D: CD20/19 more than 50%. Patients' backgrounds, pathological diagnoses, primary lesions, etc. were also analyzed. 2) Among DLBCL cases, 76 treated with R-chemo were selected and analyzed with respect to treatment response and overall survival. Results 1) Diagnoses: DLBCL 128, Follicular lymphoma 58, MALT 7, CLL 4 and so on. Among the DLBCL cases, immunohistochemistry indicated six (4%) were CD20-negative and three were CD20-positive; the ages in the CD20-negative DLBCL group tended to be high (74.28 vs 64.36, p=0.06, t-test). Weak CD20 expression was observed in 15 cases (B: 4, C:11). No statistically significant differences were seen with respect to gender, IPI, clinical stage, biopsy lesion, CD5 expression or Karyotype. No FL cases were CD20-negative, but two ( 3.4%) showed low CD20 expression. 2) Kaplan-Meier analysis of 76 cases of DLBCL treated with R-Chemo showed a significantly lower overall survival for Group A, (CD20-negative) while there was no significant difference in overall survival of Groups B+C(CD20-weak) and D(CD20-normal). Our results indicate that even patients with lower levels of CD20 expression in B-cell lymphoma may respond favorably to anti-CD20 therapy. Further studies will be necessary to explore this possibility. Disclosures No relevant conflicts of interest to declare.

Understanding CD20 Regulation By Loss-Of-Function RNAi Screen

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 4221-4221
Author(s):  
Mikolaj Slabicki ◽  
Leopold Sellner ◽  
Alexander Jethwa ◽  
Tatjana Stolz ◽  
Srinivas Mamidi ◽  
...  
Keyword(s):  
B Cell ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Rnai Screen ◽  
Lymphoma Cell ◽  
Raji Cells ◽  
Expression Levels ◽  
Cd20 Expression ◽  
Anti Cd20 ◽  
Druggable Targets

Abstract Introduction CD20 is a cell surface glycoprotein, encoded by the MS4A1 gene, which is highly expressed on most B-cells. Although CD20 is suggested to be involved in calcium signaling, its exact function is unknown. The monoclonal antibody rituximab, which targets CD20, has revolutionized the treatment of B-cell lymphoma. Despite the widespread use of CD20 antibodies across lymphoma subtypes, little is known about the endogenous regulation of CD20. The tight correlation between CD20 expression and responsiveness to CD20 antibody suggests that increasing CD20 expression levels could improve rituximab sensitivity. This could be particularly useful for B-cell lymphoma with low CD20 surface expression (e.g. chronic lymphocytic leukemia). The main goal of the project is to dissect and understand the CD20 regulation using an unbiased RNAi approach and to exploit this knowledge to improve the efficacy of anti-CD20 therapy. Methods In order to discover novel regulators of CD20 expression, we performed a genome-wide RNAi screen. The shRNA library targets over 5000 mRNAs, with 5 to 6 shRNAs per target. The CD20 regulatome was studied in a Burkitt lymphoma cell line (Raji) characterized by medium expression of CD20. Results MS4A1 was the most significant screen hit that decreased CD20 surface levels with three shRNAs and served as positive control. Based on stringent selection criteria, we identified hits involved in diverse molecular mechanisms such as signaling, trafficking, chromatin remodeling and cell membrane composition. In total, 21 genes targeted with two non-overlapping shRNAs were selected for validation: 12 decreasing and 9 increasing CD20 levels. For every gene, two shRNAs were synthesized and cloned into shRNA expression vectors. Every shRNA was investigated in separate experiments for its effect on CD20 expression levels on Raji cells. We were able to validate and confirm the influence of those genes on CD20 phenotype on Raji cells, as well as on other B-cell lymphoma cell lines (SuDHL5, BL2 and BL60). The group of genes decreasing CD20 expression can provide an insight into physiological regulation and the machinery involved in CD20 trafficking and processing. More relevant from a therapeutic viewpoint are genes where silencing increases the expression of CD20. In order to investigate a potential therapeutic synergy of our hits with Rituximab, we investigated complement-mediated lysis triggered by Rituximab in vitro after silencing of several hits. In this assay we observed direct correlation between CD20 surface levels with the sensitivity towards Rituximab for our hits: increased CD20 levels led to more Rituximab induced lysis (up to two fold increase), and vice versa. One of the main aims of the screen was the discovery of druggable targets that can be potentially used in combination therapy with Rituximab. Indeed, a chemical inhibitor targeting one of our screen hits was able to increase CD20 expression levels on Raji cells. Conclusion With an unbiased shRNA screen we identified potent regulators of CD20 expression levels. Our approach led to the discovery of novel druggable targets, which modulate CD20 levels. This may provide the rationale for novel combinatory therapies, which might improve the efficiency of anti-CD20 therapy in B-cell lymphoma. Disclosures: No relevant conflicts of interest to declare.

scholarly journals CD20 Is an Unstable Target in Primary-Refractory High-Grade Lymphomas

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 1608-1608
Author(s):  
Ryan N Rys ◽  
Dominique Geoffrion ◽  
Christopher Rushton ◽  
Miguel Alcaide ◽  
Raoul Santiago ◽  
...  
Keyword(s):  
B Cell ◽  
Board Of Directors ◽  
Research Funding ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
High Grade ◽  
Advisory Committees ◽  
Increased Risk ◽  
Cd20 Expression ◽  
Anti Cd20

Introduction: A third of patients with diffuse large B cell lymphoma (DLBCL) are not cured with rituximab, cyclophosphamide, doxorubicin, vincristine and prednisone (RCHOP). Approximately 20% of DLBCLs will lose CD20-protein expression (CD20-neg) at the time of relapse. The incidence of CD20-neg relapses in other aggressive B cell lymphomas is unknown. CD20 is not only targeted by rituximab but other antibody-based therapies that are being investigated in salvage regimens. We hypothesized that prolonged exposure to anti-CD20 containing regimens may lead a CD20-neg relapse. Our goal was to determine the clinical and genetic factors associated with loss of CD20 expression in high-grade lymphomas treated with curative intent. Method: We consented 374 patients with B cell high-grade lymphomas that were treated with RCHOP or more intensive regimens at the time of diagnosis or had a histological transformation from a prior indolent lymphoma (TLy). We recorded the baseline clinical characteristics, histological diagnosis, date of first relapse and the number of treatment regimens prior to their second biopsy. CD20 expression and cell of origin (COO) were determined by immunohistochemistry and, in the latter, using Hans criteria. We performed targeted sequencing of 63 lymphoma-related genes, including MS4A1, the gene that encodes CD20. Sequencing was performed using circulating tumor DNA in the plasma or DNA from the tumor biopsy, both obtained at the time of relapse. Results: Relapse occurred in 170/374 (45%) of patients: 102/253 DLBCL, 55/96 TLy, 6/16 primary mediastinal B cell lymphoma (PMBCL) and 7/9 high grade B cell lymphomas (HGBL) with or without translocations in MYC and BCL2 or BCL6. The median age at diagnosis was 62 years old, 54% were male and 85% had an elevated international prognostic index of ≥ 2. Of these, 104 had a biopsy taken at first (47%) or subsequent relapse (53%) to confirm the diagnosis or performed in the context of a clinical trial. CD20 could be assessed in 100 cases, of which 26 had CD20-neg lymphoma cells: 15/56 (27%) of DLBCL, 7/38 (18%) of TLy, 2/3 (66%) PMBCL and 2/3 (66%) HGBL. Relapsed PMBCL and HGBL combined, appeared to have an increased risk of CD20 negativity at relapse compared to DLBCL and TLy (p=0.043). A GCB phenotype in DLBCL was present in 35% of cases and was not associated with CD20 status. The mean number of therapies given before the second biopsy was similar in both groups (CD20+ = 2.2 and CD20-neg = 2.7, p=0.2). In fact, 11/26 (44%) of CD20-neg cases had biopsies taken after RCHOP alone. Additional chemo-immunotherapy (range 2 to 8) did not increase the risk of having a CD20-neg relapse (p=0.5), suggesting that unlike follicular lymphoma, the emergence of CD20-neg cells occurs early after rituximab exposure in high-grade lymphomas. Supporting this hypothesis, patients with a CD20-neg relapse had a shorter progressive free survival (PFS) after RCHOP (1,7 vs 3,2 years, p=0.025). Patients with primary treatment failure, defined here as a PFS of < 1 year, had a significantly increased risk of having a CD20-neg relapse (hazard ratio 7.9, p= 0.005). Sequencing was performed in 75/100 patients. MS4A1 mutations were present in 16% of CD20-neg cases, while none were present in the CD20+ cases (p=0.003). There was no significant difference in the mutation rate of TP53 (47%) or histone-modifying genes based on CD20 expression status. Conclusion: Decreased CD20 expression occurs early in high-grade lymphomas under the selective pressure of RCHOP, 16% of which are a consequence of MS4A1 mutations, suggesting that other mechanisms also modulate CD20 expression. In patients with a PFS of < 1 year, a repeat biopsy would be recommended if primary anti-CD20-targeted therapy is considered. Disclosures Assouline: F. Hoffmann-La Roche Ltd: Consultancy, Honoraria; Abbvie: Consultancy, Honoraria; Janssen: Consultancy, Honoraria, Speakers Bureau; Pfizer: Consultancy, Honoraria, Speakers Bureau. Johnson:Abbvie: Consultancy, Employment, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Roche: Consultancy, Employment, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel fees, gifts, and others, Research Funding; BMS: Consultancy, Honoraria; Merck: Consultancy, Honoraria; BD Biosciences: Other: Provided a significant proportion of the antibodies used in this project free of cost.; Seattle Genetics: Honoraria; Lundbeck: Employment, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel fees, gifts, and others, Research Funding.

scholarly journals Spectrum of common Hodgkin lymphoma and non-Hodgkin lymphomas subtypes in Zambia: a 3-year records review

2021 ◽  
Vol 40 (1) ◽  
Author(s):  
Pascal Polepole ◽  
Victor C. Mudenda ◽  
Sody M. Munsaka ◽  
Luwen Zhang
Keyword(s):  
B Cell ◽  
Hodgkin’S Lymphoma ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
University Teaching ◽  
Hodgkin's Lymphoma ◽  
World Health ◽  
Exact Test ◽  
Significant Difference ◽  
Health Organization

Abstract Background Lymphomas usually present with different occurrence patterns across different geographical locations, but their epidemiology in Zambia is yet to be extensively explored. Objectives To study the spectrum of lymphoma subtypes prevalent within the Zambian population. Methods Histopathological records with suspected lymphoma at the University Teaching Hospital (UTH) in Lusaka from the year 2014 to 2016, diagnosed based on the 2008 World Health Organization (WHO) criteria were reviewed. The analysis was done in terms of type, sex, age, and site of biopsy; and Fisher’s exact test was used for significance testing. Results During the study period (2014-2016), there were more B cell neoplasms {222 (92.5%)} than T cell neoplasms {18 (7.5%)}. Non-Hodgkin’s lymphoma (NHL) was seen in 191 (79.6%) whereas classic Hodgkin’s lymphoma (CHL) was seen in 39 (16.3%). Burkitt’s lymphoma (BL) and diffuse large B cell lymphoma (DLBCL) showed equal proportions {17.5% of all lymphoma cases (42/240) each}, as the most prevalent subtypes of NHL whereas marginal zone B cell lymphoma was the rarest subtype with 1.4% (4/240). For CHL, mixed cellularity and lymphocyte rich subtypes (4.6% of all lymphoma cases) were the most common subtypes. There was a statistically significant difference in the occurrences of lymphoma subtypes across different age categories (p = 0.002). Conclusion Zambia has a diverse lymphoma subtypes population, affecting a relatively young population. The data from this study will serve as a baseline for improved health care provision and more robust future studies.

Fas or Fas Ligand Expression Can Determine the Clinical Outcome of Germinal Center Type in Diffuse Large B Cell Lymphoma.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 3267-3267
Author(s):  
Yasushi Kojima ◽  
Hisashi Tsurumi ◽  
Naoe Goto ◽  
Michio Sawada ◽  
Toshiki Yamada ◽  
...  
Keyword(s):  
Overall Survival ◽  
B Cell ◽  
Germinal Center ◽  
Fas Ligand ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Large B Cell Lymphoma ◽  
Significant Difference ◽  
Type 3 ◽  
Large B Cell

Abstract In recent years, diffuse large B cell lymphoma (DLBCL) has been classified by a cDNA microarray, an oligonucreotide microarray, or a tissue microarray. From the prognostic point of view, DLBCL consists of germinal center B-cell-like (GC) type, activated B-cell-like (ABC) type and type 3. ABC type and type 3 can be collectively categorized as non-GC (NGC) type. GC type has favorable prognosis compared with NGC type. Escape from apoptosis is considered to be an important mechanism for the progression of lymphoma. Fas is the major protein which leads to apoptosis by binding with Fas-ligand (FasL). We evaluated the prognostic significance of such markers as CD10, Bcl-6, MUM1, Fas and FasL, as well as GC or NGC type with paraffin embedded sections from 69 DLBCL patients immunohistochemicaly. The patients were 40 men and 29 women with median age of 67 years old (range, 20–82 years old). The median follow-up of surviving patients was 43 months. The 3-year OS for the entire group was 56%. There was no significant difference in sex, age, clinical stage, lactate dehydrogenase, or International Prognostic Index between GC and NGC type. Expression of CD10 was seen in 29% (20 of 69 of the patients), Bcl-6 in 27% (19 of 69), MUM1 in 27% (19 of 69), Fas in 51% (36 of 69), and FasL in 50% (35 of 69). We divided 69 DLBCLs to 26 GC type (CD10 positive or Bcl-6 positive and MUM1 negative) and 43 NGC type (the other). Positive CD10 was the best marker to indicate favorable overall survival (p=0.0156). GC type had tendency to have better overall survival than NGC type, though it was not significant (p=0.0723). Although Fas or FasL expression was not significant for overall survival in all DLBCL, it predicted significantly a longer over all survival (Fas; p=0.0021, FasL; p=0.0165) in GC type. These results may suggest that the presence of a subtype of DLBCL in which Fas/FasL system works effectively. This group is approximately 20% of DLBCL and mainly belongs to the GC type. Fas expression in GC type of DLBCL may predict the prognosis and be useful to choose the appropriate therapy. Furthermore, CD10 was more significant than GC type and, thus, we may need to build the strict consensus for GC type.

41 Optimization of an ultrasensitive, quantitative immunoassay for detection of CD20 in non-hodgkin’s lymphoma (NHL) FFPE samples

2020 ◽  
Vol 8 (Suppl 3) ◽  
pp. A42-A42
Author(s):  
Apollina Goel ◽  
Michael Ross ◽  
Jeanette Rheinhardt ◽  
Peter Duval ◽  
Michael Maker ◽  
...  
Keyword(s):  
Flow Cytometry ◽  
B Cell ◽  
Dynamic Range ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
B Lymphoma ◽  
Large B Cell Lymphoma ◽  
Assay Performance ◽  
Cd20 Expression ◽  
Large B Cell

BackgroundCD20, a membrane B cell marker, is expressed on the majority of mature B cell neoplasms, including diffuse large B cell lymphoma and follicular lymphoma. Importantly, CD20 is the target of rituximab as well as autologous T cell and BiTE® therapies in clinical development. Studies show that one mechanism of resistance to rituximab-containing therapies is downregulation of CD20.1 2 Development of an assay that provides highly sensitive and accurate detection of CD20 levels in the tissue context may help to assess whether there is a minimum CD20 threshold associated with response to rituximab or other CD20-targeted therapies. Here, we describe the development of a novel Quanticell™ assay for sensitive and quantitative detection of CD20 expression in formalin-fixed paraffin-embedded (FFPE) biopsy samples from NHL patients.MethodsA CD20 (Abcam, clone SP32) Quanticell-based assay, which utilizes Konica Minolta’s novel fluorescent phosphor-integrated dots (PIDs)3 was optimized on a panel of B lymphoma cell lines. Flow cytometry was performed to benchmark assay performance. Next, a human B lymphoma tissue microarray (TMA, n=39 cores) was stained using DAB-IHC to evaluate CD20 expression. Tumor cores (n=10) showing CD20highCD19high expression by DAB-IHC and immunofluorescence (IF)-IHC were selected for further evaluation. Human tonsil tissue was used to assess CD20 assay performance as a Quanticell singleplex or duplexed with CD19 IF-IHC. The TMA was stained with CD20 Quanticell plus CD19-AF488 to measure CD20 expression on a per cell basis. To assess sensitivity of CD20 Quanticell detection, a CD19 negative non-B cell core was analyzed. CD20 expression determined by Quanticell was compared to results generated with a commercially available method enabling digital profiling of CD20 protein in FFPE sections.ResultsAnalytical comparison between the Quanticell assay and flow cytometry on cell lines showed strong concordance between the two methods (CD20 Quanticell score versus CD20 receptor number). The Quanticell method demonstrated a broader dynamic range in CD20 expression in the TMA samples compared to DAB-IHC. Both the Quanticell and digital protein detection assays appropriately clustered cores into CD20low and CD20high categories. Notably, the CD20 Quanticell assay demonstrated the ability to measure CD20 expression accurately and precisely over a broader dynamic range when compared to the digital method.ConclusionsRelative to DAB IHC, the novel CD20 Quanticell assay provides significantly enhanced detection and quantification of CD20 in FFPE tissue samples. This technology may be useful to assess whether there are critical antigen densities associated with response to CD20-targeting therapies.AcknowledgementsThe authors gratefully acknowledge technical assistance from Ankit Gandhi and Marie Zamanis. The authors also thank Sean Gerrin for technical writing review.Trial RegistrationN/AEthics ApprovalN/AConsentN/AReferencesJohnson NA, Boyle A, Bashashati A, et al. Diffuse large B-cell lymphoma: Reduced CD20 expression is associated with an inferior survival. Blood; 2009;113:3773.Rasheed AA, Samad A, Raheem A, et al. CD20 expression and effects on outcome of relapsed/refractory diffuse large B cell lymphoma after treatment with Rituximab. Asian Pac J Cancer Prev 2018; 19: 331Gonda K, Watanabe M, Tada H, et al. Quantitative diagnostic imaging of cancer tissues by using phosphor-integrated dots with ultra-high brightness. Sci Rep 2017;7:7509.

scholarly journals Clinical, Hematological, Genetic, and Pathological Significance in Newly Diagnosed High Grade B-Cell Lymphoma and Diffuse Large B-Cell Lymphoma

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 5339-5339
Author(s):  
Qingyuan Qu ◽  
Lingyan Zhang ◽  
Chao Xue ◽  
Xueling Ge ◽  
Xiao Lv ◽  
...  
Keyword(s):  
B Cell ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
World Health ◽  
High Grade ◽  
Newly Diagnosed ◽  
Significant Difference ◽  
Ann Arbor ◽  
Ebv Dna ◽  
Bcl6 Expression

Background: According to the 2016 revised World Health Organization (WHO) Classification of Lymphoid Tumors, high grade B-cell lymphoma (HGBL) has been delimited as a new category with two subgroups: HGBL with rearrangements of MYC and BCL2 and/or BCL6 (so-called "double/triple hit lymphoma), and HGBL-NOS (HGBLs with features intermediate between DLBCL and Burkitt lymphoma). Retrospective data indicated many patients with HGBL diagnosed at an advanced stage and often have extremely poor outcome even if they received intensive chemotherapy. The accurate genetic and pathological mechanism of this high-risk lymphoma remains uncertain. For HGBL, traditional scoring may not be systematic enough and has limited reference value, more accurate prognostic grouping indicators are needed. The aim of this study was to evaluate the clinicopathological significances in newly diagnosed HGBL and DLBCL. Several clinical and hematological indexes in concert with Fluorescence in situ hybridization (FISH) rearrangement and Immunohistochemistry (IHC) expression profiles of biomarkers between HGBL and DLBCL will also be analyzed. Methods: We reviewed 52 patients diagnosed as HGBL or DLBCL in our hospital from 2017 to 2018 retrospectively. The clinical and hematological characteristics of the patients including age, gender, Ann-Arbor stage, B symptoms, serum LDH levels, β2-microglobulin (β2-MG), peripheral EBV-DNA copies, white blood cell (WBC), absolute neutrophil count (ANC), absolute lymphocyte count (ALC), and IPI score were collected. FISH detection was done in each patient to identify whether the patient had MYC, BCL2, and BCL6 rearrangement. The expressions of the above three indexes were done by IHC as well. NLR (neutrophil to lymphocyte ratio) was definited as ANC/ALC ratio. Results: A total of 52 newly diagnosed patients were included in this study, including 34 (65.4%) males and 18 (34.6%) females. The median age at diagnosis was 54.1 years old (range, 15-88 years), and 22 (42.3%) of them were more than 60 years old. Six patients were classified into the HGBL category and 2 of them were HGBL-NOS subgroup. Twenty-five patients were MYC, BCL2, or BCL6 rearrangement single-positive. Among them, MYC, BCL2, and BCL6 rearrangement were detected in 13.5%, 7.7%, and 30.8% of 52 patients respectively.MYC (cut-off value >40%), BCL2 (cut-off value >50%), and BCL6 expression was found in 48.1%, 50%, and 65.4% of 52 patients, respectively. Among all of the patients, 32.7% (17/52) CD5 positive and 73.1% (38/52) MUM1 positive. 30.8% (16/52) of them were at stage Ⅰ/Ⅱ and 69.2% (36/52) of them were at stage Ⅲ/Ⅳ. 53.8% (28/52) of the patients had a high blood LDH level, 26.9% (14/52) showed an elevation of β2-MG level (>3mg/L) and 38.5% (20/52) presented high IPI score (IPI>2). The baseline clinical, hematological, and pathological characteristics are described in Table 1, 2. 3. With Pearson's Chi-square Tests analysis, the IPI score was significantly higher in patients older than 60 years old (P<01). Patients with the rearrangement of both BCL2 and BCL6 as well as CD5+ tend to have a higher Ki 67 ratio (P=0.045) and the same thing happened to patients with both MYC and BCL6 expression (P=0.049). By the combination of either a positive gene rearrangement or a positive IHC marker (CD5 or MUM 1), there was a close association between any of the above with high β2-MG (P=0.024) and pheripheral EBV DNA copoies (P=0.012). Besides, the triple positive rearrangements combined with CD5 positive is associated with a higher NLR (P=0.027). Conclusions: In this study, we validated the prognostic value of several clinical, hematological, genetic, and pathological indexes in newly diagnosed HGBL and DLBCL. We found that if there's only one rearrangement gene or IHC marker (CD5 or MUM 1) positive, there was no significant difference between these alterations and some classic evaluation indexes such as serum LDH and Ann-Arbor stage. Patients with BCL2 + BCL6, or MYC + BCL6, or triple positive arrangement might have a more aggressive disease progression if positive CD5 expression could be detected at the same time. In the future, we plan to further evaluate if NLR has any correlation with the clinical outcome of patients with double-/triple-hit lymphomas or double-/triple expression lymphomas. More data from larger patient subset are needed to corroborate these findings. Disclosures No relevant conflicts of interest to declare.

MicroRNAs Specific for Immune-Privileged Diffuse Large B-Cell Lymphoma.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 1566-1566
Author(s):  
JanLukas Robertus ◽  
Geert Harms ◽  
Tjasso Blokzijl ◽  
Daphne de Jong ◽  
Marije Booman ◽  
...  
Keyword(s):  
B Cell ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Heterogeneous Group ◽  
Stage I ◽  
Expression Level ◽  
Expression Levels ◽  
Significant Difference ◽  
Privileged Site ◽  
Large B Cell

Abstract Introduction Primary diffuse large B-cell lymphomas (DLBCL) constitute a heterogeneous group of tumors with a great diversity in both clinical presentation and outcome. Besides nodal DLBCL, about 40% of these tumors present in different extranodal sites, both immune privileged sites such as the testis and the central nervous system (PCNSL) but also non immune privileged sites such as bone, stomach, skin and mediastinum. Remarkably each of these sites show a marked divergence in biological behavior. Recent studies have shown that certain non-coding short RNAs (22nt) called miRNAs may play a role in the pathogenesis of DLBCL. These miRNAs posttrancriptionally down regulate expression of genes. Aim of study To examine the expression levels of selected miRNAs in different DLBCL sites. Methods and Materials 51 cases of Ann Abour stage I and II primary DLBCL were divided into 4 groups; 19 nodal cases, 11 non-immune privileged site-associated (non-IP) extranodal cases, 9 PCNSL, and 12 testicular DLBCL. Each case was classified GCB or non-GCB using the algorithm as described by Hans et al. 13 miRNAs were selected from current literature on the basis of their involvement in B-cell lymphoma (miR-15, -16, -21, -221, -155, - 181a, -18a, -19, -20a, 17-3p, -17-5p and -92). The expression levels of the mature microRNAs were determined by qRT-PCR using Taqman miRNA assays. Results were compared by using 2−ΔCt and 2−ΔΔCt. Differences in expression levels between the four groups was tested using ANOVA. Results Of the selected microRNAs, miR-127, miR-17-5p and miR-221 show a significant difference in expression level between the immune privileged site-associated DLBCL (IP-DLBCL) and nodal DLBCL. Both miR-17-5p (p=0.0003) and miR-221 (p=0.0032) show an increased expression level in PCNSL compared to nodal DLBCL and miR-127 shows a significant increased level in testicular DLBCL compared to nodal (p=0.0011) and non-IP (p=0.0393) DLBCL. Also of interest is the fact that miR-17-5p and miR-127 show a significant difference in the level of expression between both PCNSL and testicular DLBCL. MiR-155 shows no significant difference in expression levels between nodal and extranodal DLBCL. Analysis on the basis of GCB and non-GCB classification is currently being undertaken. Conclusion In PCNSL miR-17-5p and miR-221 are specifically increased whereas miR-127 shows a specifically higher expression in testicular DLBCL when compared to non-IP and nodal DLBCL. Also PCNSL and testicular DLBCL differ in expression of miR-17-5p and miR-127. In contrast to previous reports miR-155 does not show any significant difference between nodal and extranodal groups. This may be caused by the selection of stage I or II primary DLBCL in contrast to previous publications which used a more heterogeneous group of DLBCL.

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