Homo sapiens
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA111339 | ENA |
REPOSITORIES: ENA
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Project description:Nodal marginal zone lymphoma (NMZL) is a small B cell neoplasm whose molecular pathogenesis is still essentially unknown and whose differentiation from other small B cell lymphomas is hampered by the lack of specific markers. We have analyzed gene expression, miRNA profile and copy number data from 15 NMZLs. For comparison, 16 follicular lymphomas, 9 extranodal marginal zone lymphomas, 8 reactive lymph nodes and B cell subtypes were included. The results were validated by qRT-PCR in an independent paraffin-embedded series including 61 NMZLs. NMZL signature showed an enriched expression of gene sets identifying interleukins, integrins, CD40, PI3K, NFkB and TGF-Beta; and included genes expressed by normal marginal zone cells and memory B cells. The most highly overexpressed genes were SYK, TACI, CD74, CD82 and CDC42EP5. Genes linked to G2/M and germinal center were downregulated. Comparison of the gene expression profiles of NMZL and FL showed enriched expression of CHIT1 and TACI in NMZL, and BCL6, LMO2 and CD10 in FL. NMZL displayed increased expression of miR-223 and let-7f, while FL strongly expressed miR-494. Our study identifies new candidate diagnostic molecules for NMZL and reveals survival pathways activated in NMZL. microRNA-expression profiling was conducted in a series of 40 B-cell non-Hodgkin lymphoma patients (NMZL, and FL). Six lymph nodes with reactive lymphoid hyperplasia (RLN) were used as controls
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Project description:Expression data of human B lymphocytes from follicular lymphoma lymph nodes (FL)
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Project description:Angiogenesis plays a key role in tumor metastasis. Many genes may act in this process including formation of vessels, immune evasion,etc. Different gene expression profiles between lymphoma endothelium cells and reactive lymph node-derived endothelium cells may uncover these genes. And intensive mechanism researches on such key genes may explain the mechanisim of tumor-specific angiogenesis and help to explore effective treatment strategies to prevent/reverse tumor metastasis. We use microarrays to detail gene expression profiles of human lymphoma endothelium and reactive lymph node-derived endothelium. Lymph nodes were taken from surgery samples of cases pathologically diagnosed DLBCL (diffuse large B-cell lymphoma), PTL (peripheral T cell lymphoma) and reactive lymph nodes. The pure endothelium cells were isolated by LCM after immunohistochemical staining of CD34. We found Tim-3 was preferentially expressed on lymphoma-derived ECs via different expression profiles between lymphoma ECs and reactive lymph node-derived ECs. Intensive researches were carried out on Tim-3-expressing -ECs and we found that Tim-3 -expressing-Ecs may play important role on EC-mediated tumor evasion.
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Project description:We have previously shown that Tregs infiltrating follicular lymphoma lymph nodes (FLN) are quantitatively and qualitatively different than those infiltrating normal and reactive nodes (NLN, RLN, respectively). To gain insight into how such Treg populations differ, we performed RNA sequence (RNAseq) analyses on flow sorted Tregs from all three sources. We identify several molecules that could contribute to the observed increased suppressive capacity of FLN tregs, including upregulation of CTLA-4, IL-10, and GITR, all confirmed by protein expression. In addition, we identify, and confirm functionally, a novel mechanism by which Tregs target to and accumulate within a human tumor microenvironment, through the down regulation of S1PR1, SELL (L-selectin) and CCR7, potentially resulting in greater lymph node retention. In addition we identify and confirm functionally the upregulation of CXCR5, CXCL13 and IL-16 demonstrating the unique ability of the follicular derived Tregs to localize and accumulate within not only the malignant lymph node, but also localize and accumulate within the malignant B cell follicle itself. Such findings offer significant new insights into how FLN Tregs may contribute to the biology of follicular lymphoma and identify several novel therapeutic targets.
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