Project description:Mantle cell lymphoma (MCL) is an aggressive neoplasm with poor outcome. However, some patients have an indolent disease (iMCL) and may not require intensive treatment at initial diagnosis. Diagnostic criteria to recognize these patients are not available. We hypothesized that the analysis of the genetic and expression features of the tumors may help to identify patients with an indolent clinical evolution and provide biomarkers that could be used in the clinical setting. Seven patients with an iMCL that did not require chemotherapy for more than 2 years were compared to 15 conventional MCL (cMCL) that needed systemic therapy at diagnosis. MCL were compared with other leukemic lymphoid neoplasms including 17 CLL, 7FL, HCL and 2HCLv.
Project description:Of the 142 patients enrolled in Study CHRONOS-1, an open-label, single-arm, Phase II study evaluating the efficacy and safety of single-agent copanlisib in patients with relapsed or refractory, indolent B-cell lymphoma (NCT01660451; Part B), 96 archival formalin-fixed paraffin-embedded tumor tissues were collected under relevant consent and available for tumor macro-dissection, mRNA extraction and gene expression profiling using Affymetrix GeneChip Gene ST 1.0 Arrays (AltheaDx, Inc., San Diego, CA, USA). Of these, only 78 samples were with high quality and passed Affymetrix positive versus negative controls AUC ≥ 0.62. Affymetrix CEL files were processed with RMA (R package affy) using a custom CDF from Brainarray (version 20.0.0). 71 patients with indolent non-Hodgkin lymphoma (iNHL), including 54 with follicular lymphoma (FL), had both response data and evaluable gene expression data with high quality array data sets (array positive versus negative controls AUC ≥ 0.62) and were included in this biomarker analysis. In this study, with the exception of subject # 16349B-53, for which expression values were averaged from three equal aliquots that were amplified and scanned on 3 separate days in order to control for day-to-day batch effect, there was only one sample per subject. Affymetrix raw data (CEL files) and the gene expression matrix generated with RMA for the 78 high quality tumor samples are submitted.
Project description:Mantle cell lymphoma (MCL) is an aggressive neoplasm with poor outcome. However, some patients have an indolent disease (iMCL) and may not require intensive treatment at initial diagnosis. Diagnostic criteria to recognize these patients are not available. We hypothesized that the analysis of the genetic and expression features of the tumors may help to identify patients with an indolent clinical evolution and provide biomarkers that could be used in the clinical setting.
Project description:Primary outcome(s): a)To study the association of baseline vitamin D level with Overall Response Rate(ORR) in patients with newly diagnosed lymphoma.
b)To study the effect of vitamin D supplementation on Overall Response Rate (ORR) in the vitamin D deficient patients with newly diagnosed lymphoma.
Timepoint: August 2018 to May 2020
Project description:BACKGROUND AND OBJECTIVES: Low-grade B-cell lymphomas include several subtypes of tumors with different degrees of histological, biological or clinical features. Differential diagnosis is frequently compromised by the lack of specific cytogenetic or molecular features. As a consequence, therapies remain in many lymphoma types largely based in common protocols with largely variable success. Our objectives were to describe and to compare the genomic profile of a series of samples from the most prevalent low-grade lymphoma subtypes; all of them systematically analyzed with the same approach. DESIGN-AND-METHODS: We carried out a high-resolution genomic DNA analysis (44K probes) in 87 low grade B cell lymphoma tumor samples that unambiguously presented the clinical picture, analytical features, and peripheral blood morphology and phenotype described for each entity. RESULTS: The genomic integrity of the samples was heavily compromised (80% of the tumors presented at least one aberration). This phenomenon also involved lymphoplasmocytic and marginal zone lymphomas that have not been previously studied by this genomic approach. New aberrations have been described for almost every subtype. We have also generated reports of the extension of the genomic instability, detecting distinct patterns of genomic instability within subtypes. INTERPRETATION-AND-CONCLUSIONS: The genomic profile of each subgroup showed substantive differences. The bioinformatic analysis of the data detected a set of new aberrations which were present in the majority of the subgroups and that pointed out to specific pathways, such as NF-kB (gains that involved REL, BCL11A and COMMD1) or DNA repair checkpoint pathways (deletion of 16q24 involving CDT1). Keywords: Comparative Genomic Hybridization - array; Genomic Instability
Project description:Follicular lymphoma is the most common indolent non-Hodgkin's lymphoma involving germinal centre B cells, with a subset of patients undergoing transformation to a diffuse large B-cell lymphoma (DLBCL) morphology for which the clinical outcomes are poor. To elucidate the differences in copy number profiles between FL and tFL groups, we performed Affymetrix SNP 6.0 Array analysis on 31 paired FL-tFL cases. We wanted to identify and compare recurrent somatic copy number alterations (CNAs) between the two groups (FL vs. tFL). In addition, the concordance and discordance in the copy neutral loss of heterozygosity (cnLOH) between the two groups were also investigated to identify recurrent target gene regions.
Project description:Vitamin D deficiency has been associated with decreased overall survival in patients with diffuse large B-cell lymphoma treated with rituximab. Natural killer cell-mediated antibody-dependent cytotoxicity is one of the main mechanisms of action of rituximab, and it has been shown to be enhanced after in vivo vitamin D supplementation. We aimed to explore molecular mechanisms behind these findings using whole transcriptome analysis of natural killer cells after vitamin D supplementation
Project description:Epidemiological data show that the immune system may control or promote emergence and growth of a neoplastic lymphomatous clone. Conversely, systemic lymphomas, especially myeloma and CLL, are associated with clinical immunodeficiency. This prospective controlled study demonstrates substantially reduced circulating T helper cells, predominantly naive CD4+ cells, in patients with non-leukemic follicular and extranodal marginal zone lymphomas, but not in monoclonal gammopathy and early CLL. These numerical changes were correlated with a preactivated phenotype, hyperreactivity in vitro, presenescence, and a Th2 shift of peripheral T helper cells. No prominent alterations were found in the regulatory T cell compartment. Gene expression profiling of in vitro-stimulated CD4+ cells revealed an independent second alteration of T helper cell physiology which was most pronounced in early CLL but also detectable in FL/eMZL. This pattern consisted of downregulation of proximal and intermediate T-cell receptor signaling cascades and globally reduced cytokine secretion. Both types of T cell dysfunction may contribute to significant immunodeficiency in non-leukemic indolent B-cell lymphomas as demonstrated by refractoriness to hepatitis B vaccination. The precise definition of systemic T cell dysfunction serves as the basis to study its prognostic impact, its relationship to the established influence of the lymphoma microenvironment, and its therapeutic manipulation 8 samples from FL/eMZL patients, 7 samples from CLL patients, 5 samples of MGUS patients, 5 MALT, 16 healthy controls