Search results for "B-CELL"

Renal tubular epithelial cell-derived BAFF expression mediates kidney damage and correlates with activity of proliferative lupus nephritis in mouse a…

2017

B-cell activating factor of the tumour necrosis factor family (BAFF) is a cytokine, mainly produced by hematopoietic cells (e.g. monocytes/macrophages, dendritic cells), indispensable for B-cell maturation. The BLISS studies have demonstrated that blocking BAFF by the human monoclonal antibody belimumab is a valuable therapeutic approach in patients with clinically and serologically active systemic lupus erythematosus (SLE). However, the defined sources of BAFF, which contributes to SLE, are still unclear. Recent findings show that BAFF expression is not restricted to myeloid cells. Since lupus nephritis is the main cause of morbidity and mortality for SLE patients, the aim of this study wa…

Meta-analysis of genome-wide association studies discovers multiple loci for chronic lymphocytic leukemia

2016

Chronic lymphocytic leukemia (CLL) is a common lymphoid malignancy with strong heritability. To further understand the genetic susceptibility for CLL and identify common loci associated with risk, we conducted a meta-analysis of four genome-wide association studies (GWAS) composed of 3,100 cases and 7,667 controls with follow-up replication in 1,958 cases and 5,530 controls. Here we report three new loci at 3p24.1 (rs9880772, EOMES, P=2.55 × 10−11), 6p25.2 (rs73718779, SERPINB6, P=1.97 × 10−8) and 3q28 (rs9815073, LPP, P=3.62 × 10−8), as well as a new independent SNP at the known 2q13 locus (rs9308731, BCL2L11, P=1.00 × 10−11) in the combined analysis. We find suggestive evidence (P<5 × 10−…

The unbalanced p53/SIRT1 axis may impact lymphocyte homeostasis in COVID-19 patients

2021

Abstract Background/objectives A dysregulated inflammatory profile plays an important role in coronavirus disease-2019 (COVID-19) pathogenesis. Moreover, the depletion of lymphocytes is typically associated with an unfavourable disease course. We studied the role and impact of p53 and deacetylase Sirtuin 1 (SIRT1) on lymph-monocyte homeostasis and their possible effect on T and B cell signalling. Methods Gene expression analysis and flow cytometry were performed on peripheral blood mononuclear cells (PBMC) of 35 COVID-19 patients and 10 healthy donors (HD). Inflammatory cytokines, the frequency of Annexin+ cells among CD3+ T cells and CD19+ B cell subsets were quantified. Results PBMC from …

Genetically Determined Height and Risk of Non-hodgkin Lymphoma

2020

Although the evidence is not consistent, epidemiologic studies have suggested that taller adult height may be associated with an increased risk of some non-Hodgkin lymphoma (NHL) subtypes. Height is largely determined by genetic factors, but how these genetic factors may contribute to NHL risk is unknown. We investigated the relationship between genetic determinants of height and NHL risk using data from eight genome-wide association studies (GWAS) comprising 10,629 NHL cases, including 3,857 diffuse large B-cell lymphoma (DLBCL), 2,847 follicular lymphoma (FL), 3,100 chronic lymphocytic leukemia (CLL), and 825 marginal zone lymphoma (MZL) cases, and 9,505 controls of European ancestry. We …

Phase 1b/3 study of avelumab-based combination regimens in patients with relapsed or refractory diffuse large B-cell lymphoma (R/R DLBCL).

2017

TPS7575 Background: Approximately 50% of patients (pts) with advanced DLBCL are refractory to or relapse following first line R-CHOP therapy. Pts with R/R DLBCL have limited treatment options and a poor prognosis. This study assesses immunotherapy-based regimens containing avelumab (a fully human IgG1 anti–PD-L1 antibody) in combination with utomilumab (a novel 4-1BB agonist), azacitidine, rituximab, and/or conventional chemotherapy (CT; bendamustine) in pts with R/R DLBCL. Methods: JAVELIN DLBCL (NCT02951156) is a global, multicenter, randomized, open-label, 2-component(phase 1b followed by phase 3) study of avelumab-based combination regimens in R/R DLBCL. In phase 1b, up to 84 pts will …

SAFETY AND CLINICAL ACTIVITY OF TEMSIROLIMUS IN COMBINATION WITH RITUXIMAB AND DHAP IN PATIENTS WITH RELAPSED OR REFRACTORY DIFFUSE LARGE B-CELL LYMP…

2017

Distinct Activities of Glycolytic Enzymes Identify Chronic Lymphocytic Leukemia Patients with a more Aggressive Course and Resistance to Chemo-Immuno…

2018

A higher capacity to grow under hypoxic conditions can lead to a more aggressive behavior of tumor cells. Determining tumor activity under hypoxia may identify chronic lymphocytic leukemia (CLL) with aggressive clinical course and predict response to chemo-immunotherapy (CIT). A metabolic score was generated by determining pyruvate kinase and lactate dehydrogenase, key enzymes of glycolysis, ex vivo in primary CLL samples under normoxic and hypoxic conditions. This score was further correlated with clinical endpoints and response to CIT in 96 CLL patients. 45 patients were classified as metabolic high risk (HR), 51 as low risk (LR). Treatment-free survival (TFS) was significantly shorter in…

Dissection of DLBCL microenvironment provides a gene expression-based predictor of survival applicable to formalin-fixed paraffin-embedded tissue

2018

Abstract Background Gene expression profiling (GEP) studies recognized a prognostic role for tumor microenvironment (TME) in diffuse large B-cell lymphoma (DLBCL), but the routinely adoption of prognostic stromal signatures remains limited. Patients and methods Here, we applied the computational method CIBERSORT to generate a 1028-gene matrix incorporating signatures of 17 immune and stromal cytotypes. Then, we carried out a deconvolution on publicly available GEP data of 482 untreated DLBCLs to reveal associations between clinical outcomes and proportions of putative tumor-infiltrating cell types. Forty-five genes related to peculiar prognostic cytotypes were selected and their expression …

Expression profiles of HMGB1 on B-CLL related leukocytes contribute to prediction of relapse.

2020

The High Mobility Group Box 1 (HMGB1) is a nuclear protein that is frequently overexpressed in hematologic diseases and might be of relevance in immunogenic cancer control thus correlating with patients' (pts.) prognosis in diseases such as acute myeloid, acute lymphatic and chronic lymphocytic leukemia.Expression profiles of blasts from AML (n = 21), ALL (n = 16) and of B-lymphocytes of CLL (n = 9) pts. were analyzed for surface expression of HMGB1 using flow cytometry. Expression was quantified and correlated with clinically and prognostically relevant markers.Expression profiling of HMGB1 in blasts of AML and ALL subtypes did not show differences between primary vs. secondary disease dev…

Predictive and Prognostic Molecular Factors in Diffuse Large B-Cell Lymphomas.

2021

Diffuse large B-cell lymphoma (DLBCL) is the commonest form of lymphoid malignancy, with a prevalence of about 40% worldwide. Its classification encompasses a common form, also termed as “not otherwise specified” (NOS), and a series of variants, which are rare and at least in part related to viral agents. Over the last two decades, DLBCL-NOS, which accounts for more than 80% of the neoplasms included in the DLBCL chapter, has been the object of an increasing number of molecular studies which have led to the identification of prognostic/predictive factors that are increasingly entering daily practice. In this review, the main achievements obtained by gene expression profiling (with respect t…