Gene Expression Profiling of Diffuse Large B-Cell Lymphomas Supervised by CD21 Expression.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 2029-2029
Author(s):  
Kana Miyazaki ◽  
Motoko Yamaguchi ◽  
Miho Kimura ◽  
Shoko Ogawa ◽  
Satoshi Ueno ◽  
...  
Keyword(s):  
Overall Survival ◽  
Prognostic Factor ◽  
B Cell ◽  
Tumor Cells ◽  
Frozen Sections ◽  
B Cell Lymphomas ◽  
Poor Prognostic Factor ◽  
Signature Genes ◽  
Favorable Prognostic Factor ◽  
Large B Cell

Abstract We have reported that CD21 expression in tumor cells is a favorable prognostic factor in diffuse large B-cell lymphomas (DLBCLs)(Ogawa S, et al. Br J Haematol, 2004; 125: 180–86). In the present study, we investigated the relationship between CD21 expression and the groups of germinal center B-cell-like (GCB) DLBCLs and activated B-cell-like (ABC) DLBCLs. The diagnosis of DLBCL was made according to the WHO Classification. CD21 in tumor cells was examined by means of immunohistochemistry using frozen sections. Forty cases of DLBCLs were investigated using Agilent 44K human oligo-microarrays (Agilent Technologies, Palo Alto, CA). GCB and ABC DLBCLs were identified based on Rosenwald’s gene set (Rosenwald A, et al. N Engl J Med, 2002; 346: 1937–47). Four cases (10 %) of 40 DLBCLs were found to be GCB DLBCLs, and 36 cases ABC DLBCLs. Incidence of CD21-positive cases was 50% (2/4) in GCB DLBCLs and 39% (14/36) in ABC DLBCLs. Overall survival of 36 patient with ABC DLBCLs were shown in Fig.1. Fig. 1 Fig. 1. Signature genes to distinguish between CD21-positive and CD21-negative DLBCLs were as follows; IgM (P=0.00017), CCR6 (P=0.0011), IL7 (P=0.0017), IgK (P=0.0037), EBI2 (P=0.0066), CD24 (P=0.0099) etc. were overexpressed in CD21-negative DLBCLs, and CR2 (CD21) (P=0.0010), MKNK2 (P=0.0028), LMO2 (P=0.00478), CDKN2A (P=0.0059), PDE8B (P=0.0066) etc. were overexpressed in CD21-positive DLBCLs. In 40 cases of DLBCLs, overall survival of patients with sIgM-positive DLBCL was significantly worse than that of patients with sIgM-negative DLBCL (P=0.023). Furthermore, in 216 consecutive cases of DLBCLs analyzed by immunohistochemistry using frozen sections from 1987 to 2004, overall survival according to sIgM expression was significantly different (P=0.013). In conclusion,CD21 expression was a favorable prognostic factor in ABC DLBCLs.A top feature gene to distinguish between CD21-positive and CD21-negative DLBCLs was IgM. CD21 expression seemed to be related to the differentiation level of lymphoma cells.sIgM expression itself was a poor prognostic factor in ABC DLBCLs and in whole DLBCLs.

GCB-type is a favorable prognostic factor in primary CNS diffuse large B-cell lymphomas

2021 ◽  
Vol 83 ◽  
pp. 49-55
Author(s):  
Chelsea Marcus ◽  
Georgios A. Maragkos ◽  
Ron L. Alterman ◽  
Erik Uhlmann ◽  
German Pihan ◽  
...  
Keyword(s):  
Prognostic Factor ◽  
B Cell ◽  
B Cell Lymphomas ◽  
Favorable Prognostic Factor ◽  
Large B Cell

Serum Albumin as Prognostic Factor for Overall Survival in Rearranged MYC and BCL2/BCL6 Positive Double Hit Diffuse Large B Cell Lymphomas

2016 ◽  
Vol 16 ◽  
pp. S99
Author(s):  
Chetasi Talati ◽  
Andrew Kuykendall ◽  
Jori Kaplan ◽  
Jose Sandoval-Sus ◽  
Samir Dalia ◽  
...  
Keyword(s):  
Overall Survival ◽  
Prognostic Factor ◽  
Serum Albumin ◽  
B Cell ◽  
B Cell Lymphomas ◽  
Double Hit ◽  
Large B Cell

Tumor-collagen digital proximity signature to indicate prognosis in diffuse large B-cell lymphoma.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e19073-e19073
Author(s):  
Talha Qaiser ◽  
Matthew Pugh ◽  
Sandra Margielewska ◽  
Robert Hollows ◽  
Paul Murray ◽  
...  
Keyword(s):  
Overall Survival ◽  
Tumor Cell ◽  
B Cell ◽  
Tumor Cells ◽  
Cell Lymphoma ◽  
Prognostic Significance ◽  
B Cell Lymphoma ◽  
Automated Image Analysis ◽  
Large B Cell Lymphoma ◽  
Large B Cell

e19073 Background: Diffuse large B-cell lymphoma (DLBCL) is a heterogeneous tumor that originates from normal B-cells. Despite the use of combination chemotherapy, around 40% of DLBCL patients die (de Jonge, et al. European Journal of Cancer, 2016). Limited studies have investigated the role of collagen in the acellular tumor microenvironment. In this study, we present a novel digital signature of the proximity of tumor cells and collagen-VI (COL6) that can predict overall survival (OS) in DLBCL patients. To the best of our knowledge, this is the first study of its kind to employ automated image analysis. Methods: The proposed digital proximity signature (DPS) aggregates summary-level statistics from the entire whole slide image (WSI) and serves as a marker of regions, categorizing weak, moderate, significant, and strong tumor-collagen proximity and can be described as a surrogate for signaling. To accomplish this, we developed a novel artificial intelligence (AI) based multi-task model for simultaneous detection and classification of tumor cells and another bespoke method for automatically identifying COL6 fiber. The tumor-collagen proximity analysis was then performed by aggregating tumor cell statistics within the vicinity of COL6 fibres. Finally, the prognostic significance of DPS for OS in DLBCL was investigated with Kaplan-Meier analysis, stratifying patients into two groups based on the median of the DPS values. Results: We took WSIs of DLBCL tissue slides for 32 cases immunohistochemically stained with COL6 and Hematoxylin counterstain. The AI model for tumor cell identification achieved a high F1-score of 0.84, outperforming recent single-task learning models. Our results show that strong proximity of COL6 and tumor cells is linked to better OS in DLBCL patients ( p = 0.03). Conclusions: Our novel digitally computed COL6-tumor proximity signature shows prognostic significance for overall survival on a pilot dataset of 32 DLBCL patients. We are further validating the utility of this novel signature as a prognostic biomarker in larger cohorts of DLBCL patients.

Clinicopathologic Characteristics and Outcome of Diffuse Large B-Cell Lymphomas Presenting With an Associated Low-Grade Component at Diagnosis

2006 ◽  
Vol 24 (33) ◽  
pp. 5234-5241 ◽  
Author(s):  
Hervé Ghesquières ◽  
Françoise Berger ◽  
Pascale Felman ◽  
Evelyne Callet-Bauchu ◽  
Paul-André Bryon ◽  
...  
Keyword(s):  
Overall Survival ◽  
B Cell ◽  
De Novo ◽  
Complete Response ◽  
Progression Rate ◽  
Low Grade ◽  
Control Analysis ◽  
B Cell Lymphomas ◽  
Response To Chemotherapy ◽  
Large B Cell

Purpose Some diffuse large B-cell lymphomas (DLBCL) present at diagnosis with associated morphologic features of small B-cell non-Hodgkin's lymphoma (NHL) and may arise from the transformation of a previously unknown indolent low-grade lymphoma. The characteristics and prognosis of these particular DLBCL are not well known. Patients and Methods The strict morphologic review of consecutive DLBCL patients diagnosed over 12 years in our department (Hematology Department, Centre Hospitalier Lyon-Sud, Lyon, France) allowed to retrieve 60 DLBCL that could be have occurred from the transformation of marginal zone B-cell NHL (32 patients), follicular NHL (22 patients), and small lymphocytic NHL (6 patients). We compared them to 180 matched patients of de novo DLBCL. Results Patients median age was 55 years and presented the following clinical characteristics: poor performance status in 33%, disseminated disease in 97%, more than one extranodal site in 50%, and increased lactate dehydrogenase level in 55%. Complete remission with multidrug chemotherapy regimens was achieved in 60% of the patients, but 48% relapsed: 28% with aggressive and 20% with indolent histology, respectively. Overall survival (OS) and freedom-from-progression rates at 5 years were 57% and 33%, respectively. The matched-control analysis showed that patients with transformed NHL at diagnosis had lower complete response to chemotherapy (P = .004) and higher progression rate (P = .03), whereas no difference was observed in OS (P = .21). Conclusion Compared to de novo DLBCL, transformed NHL at diagnosis have similar overall survival but lower complete response to initial treatment and higher risk of indolent relapses.

scholarly journals A Short Mutational Hot Spot in the First Intron of BCL-6 Is Associated with Increased BCL-6 Expression and with Longer Overall Survival in Large B-Cell Lymphomas

2002 ◽  
Vol 160 (4) ◽  
pp. 1371-1380 ◽  
Author(s):  
María-Jesús Artiga ◽  
Ana-Isabel Sáez ◽  
Cristina Romero ◽  
Margarita Sánchez-Beato ◽  
Mari-Sol Mateo ◽  
...  
Keyword(s):  
Overall Survival ◽  
B Cell ◽  
Hot Spot ◽  
B Cell Lymphomas ◽  
First Intron ◽  
Large B Cell

scholarly journals Acquisition of Mannoses on the Surface Immunoglobulin Binding Site Reveals Functional Status and Cell of Origin in Diffuse Large B Cell Lymphomas

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 677-677
Author(s):  
Giorgia Chiodin ◽  
Philip Rock ◽  
Enrica Antonia Martino ◽  
Beatriz Valle Argos ◽  
Graham Packham ◽  
...  
Keyword(s):  
B Cells ◽  
B Cell ◽  
Binding Site ◽  
Tumor Cells ◽  
Antigen Binding ◽  
Cell Of Origin ◽  
B Cell Lymphomas ◽  
Antigen Binding Site ◽  
Surface Immunoglobulin ◽  
Large B Cell

Abstract Acquisition of mannosylated glycans in the surface immunoglobulin (sIg) variable region (sIgV) antigen-binding site is a unique tumor-specific structural change of certain lymphomas, including all follicular lymphomas (FL) and ~40% diffuse large B-cell lymphomas (DLBCL). Mannosylation of the sIgV allows binding to environmental lectins including DC-SIGN (Coelho V et al, PNAS 2010). SIgV engagement is generally required for survival of DLBCL cells (Young RM et al, PNAS 2015), but how sIgV mannosylation distributes and affects behavior in the two germinal center B-cell-like (GCB-like) or activated B-cell-like (ABC-like) DLBCL subsets is unknown. While the mannosylation of the sIgV is tumor specific and irreversible, there are other natural N-glycosylation sites in the sIg constant region (sIgC). In secreted IgM these are mainly fully glycosylated and that is seen in sIgM of normal B cells (Krysov S et al, Blood 2010). However, engagement of sIgM by anti-IgM leads to expression ofan immature (mannosylated) form in both tumor and normal B cells. This conversion is dynamic, and tumor B cells restore expression of sIgC with mature glycans following BCR disengagement in vitro(Krysov S et al, Blood 2010). In this study, the glycosylation patterns of sIgV and sIgC were analyzed in GCB-like (n=6) vs ABC-like DLBCL lines (n=2) and primary samples (n=8) by IGHV-D-J sequencing, DC-SIGN binding and immunoblot of the biotinylated sIg following digestion by EndoH (specific for the mannosylated sugars) or by PNGase (removes all sugars). We found acquisition of N-mannosylation sequence motifs in the IGHV-D-J transcripts of all GCB-DLBCL lines with t(14;18), indicating a likely relationship with FL. In contrast, neither of the ABC-DLBCL lines had acquired sites, confirming a separate origin. DC-SIGN binding, which is specific for mannosylated IgV structures on the tumor cells, was observed in all GCB-DLBCL and not in the ABC-DLBCL, confirming that the acquired sites were glycosylated. These results allowed us to discriminate DLBCL cases into "DC-SIGN binders" (DB-DLBCL) vs "DC-SIGN non-binders" DLBCL (NB-DLBCL). Analysis of the carbohydrate structures on the sIgC revealed that the immature form was confined to the NB-DLBCL lines (2/2), while the DB-DLBCL expressed a mature fully glycosylated form (6/6). Consistent with the nature of ABC-DLBCL, these results revealed an activated BCR status of the NB-DLBCL. This was confirmed in the 8 primary samples (5/8 DB, 3/8 NB), which expressed an immature (activated) sIgC in 3/3 NB-DLBCL and a mature sIgC in 5/5 DB-DLBCL. However, engagement of anti-IgM F(ab')2 polyclonal antibody converted the inactive sIg form of DB-DLBCL into an activated sIg with relative increase of the immature sugars. It was evident that the mannosylated sites on the sIgC were not available for DC-SIGN binding, which is confined to the sIgV sites. We verified BCR activation status by investigating constitutive phosphorylation of SYK, BTK and PLCγ2, which are recruited to the membrane upon BCR activation, prior to endosome formation (Phelan JD et al, Nature 2018), in 2 DB-DLBCL lines (NU-DHL1 and SU-DHL6) and 2 NB-DLBCL (HBL-1 and TMD8). Basal phosphorylation of SYK, BTK and PLCγ2 was higher in the NB-DLBCL, consistent with the activated status associated with an immature sIgC. Our results reveal a functional dichotomy in DLBCL, which indicates: first, the cell of origin dictates whether sIgV carries mannoses in the antigen-binding site; second, reversible sIgC mannosylation associates with activation via sIg. Interestingly, this feature of activation is in ABC-DLBCL, which lacks IgV mannosylation. It is consistent with the suggestion that occupation of the antigen-binding sites with mannoses blocks further engagement of the receptor by 'antigen'. However, acquisition of mannoses in the sIgV sites appears to confer an ability to interact with environmental lectins such as DC-SIGN, whereas the sIgC sites fail to do this, suggesting an alternative function. Clearly, the post-translational modification targets several sites in sIg. Sites in the sIgC have a similar, possibly maturational, function in normal B cells, but in tumor cells the irreversible addition of mannoses to the sIgV adds a tumor-specific function. Disclosures Packham: Aquinox: Research Funding. Forconi:Abbvie: Consultancy; Janssen-Cilag: Consultancy.

scholarly journals The Neutrophil-to-Lymphocyte Ratio Is Prognostic in Patients with Diffuse Large B-Cell Lymphoma: A Study from the Latin American Group of Lymphomas (GELL)

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 2987-2987
Author(s):  
Brady E. Beltrán ◽  
Victoria Otero ◽  
Marialejandra Torres Viera ◽  
Camila Peña ◽  
Myriam Lucía Rodriguez ◽  
...  
Keyword(s):  
Overall Survival ◽  
Prognostic Factor ◽  
B Cell ◽  
Latin American ◽  
Research Funding ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Entire Group ◽  
Large B Cell Lymphoma ◽  
Large B Cell

Abstract Introduction: Diffuse large B-Cell Lymphoma (DLBCL) is the most frequent subtype of lymphoma in the world. The IPI score is a powerful risk-stratification tool in patients with DLBCL. The neutrophil-to-lymphocyte ratio (NLR) has shown to be prognostic in patients with DLBCL in Asia, Europe and USA. The GELL is a recently formed group for the study of lymphomas in Latin America composed by large institutions from eleven countries. The aim of this study was to evaluate whether the NLR is a prognostic factor in Latin American patients with DLBCL. Methods: We included patients with a pathological diagnosis of DLBCL who were diagnosed and treated at our institution between 2012-2013. IRB approval was obtained prior to research, and pathological samples were reviewed by hematopathologists at each of the participating institutions to confirm the diagnosis. Pertinent clinicopathological data were collected through chart review and are presented using descriptive statistics. The NLR was calculated by dividing the absolute neutrophil by the absolute lymphocyte count and dichotomized in NLR≥4 and NLR<4. Survival curves were estimated using the Kaplan-Meier method and compared using the log-rank test. Univariate Cox models were fitted to evaluate hazard ratios (HR) for overall survival (OS). Results: A total of 329 patients with a diagnosis of DLBCL were included in this analysis. The median age at diagnosis was 64 years (range 18-83 years) with a slight female predominance (54%). Clinically, 59% of patients were 60 or older, 34% had ECOG >1, 29% had elevated LDH, and 70% had extranodal disease; 49% had early stage and 51% had stage III and IV. The IPI score was low risk in 36%, low-intermediate in 25%, high intermediate in 22% and high risk in 17%. 41% of patients had NLR ≥4. 89% of patients received standard R-CHOP, 2% received R-miniCHOP and 9% received other regimens. The overall response rate as 83%; 69% had complete response and 14% had partial response. The median follow-up for the entire group was 5 years (95% CI 4.9-5.4 years). The 5-year overall survival (OS) rate for the entire group was 65%. The 5-year OS rates for patients with NLR ≥4 and <4 were 59% and 71%, respectively (p=0.008). Patients with low, low-intermediate, high-intermediate and high IPI scores had 5-year OS rates of 80%, 65%, 56% and 45%, respectively (p<0.001). In the multivariate analysis, advanced stage (HR 3.1, 95% CI 1.9-5.0; p<0.001), LDH level (HR 2.2, 95% CI 1.2-4.2; p=0.016) and NLR ≥4 (HR 1.7, 95% CI 1.1-2.6; p=0.03) were statistically independent factors associated with worse OS. NLR ≥4 was an adverse prognostic factor after adjusting for IPI score (HR 1.7, 95% CI 1.1-2.6; p=0.01). Conclusion: The NLR appears as a novel and easy to use prognostic factor for OS, independent of the IPI score, in previously untreated Latin American patients with DLBCL. Our findings support the need for validation of the NLR in larger retrospective or prospective studies in patients with DLBCL. Figure. Figure. Disclosures Chiattone: Janssen: Honoraria, Research Funding. Castillo:Pharmacyclics: Consultancy, Research Funding; Janssen: Consultancy, Research Funding; Beigene: Consultancy, Research Funding; Abbvie: Consultancy, Research Funding; Millennium: Research Funding; Genentech: Consultancy.

scholarly journals High Levels of Regulatory T Cells in Blood Are a Poor Prognostic Factor in Patients With Diffuse Large B-Cell Lymphoma

2015 ◽  
Vol 144 (6) ◽  
pp. 935-944 ◽  
Author(s):  
Chen Chang ◽  
Shang-Yin Wu ◽  
Yu-Wei Kang ◽  
Kun-Piao Lin ◽  
Tsai-Yun Chen ◽  
...  
Keyword(s):  
T Cells ◽  
Prognostic Factor ◽  
Regulatory T Cells ◽  
B Cell ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Poor Prognostic Factor ◽  
Large B Cell Lymphoma ◽  
Large B Cell
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