Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0079731 (B-cell lymphoma)
 16,671 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Hodgkin's lymphoma is characterized by the combination of Reed-Sternberg (R-S) cells and a prominent inflammatory cell infiltrate. One of the intriguing questions regarding this disease is what is causing the influx of T lymphocytes into the involved tissues. We applied the serial analysis of gene expression (SAGE) technique on the Hodgkin's lymphoma-derived cell line L428 and on an Epstein-Barr virus (EBV)-transformed lymphoblastoid B-cell line. A frequently expressed tag in L428 corresponded to the T-cell-directed CC chemokine TARC. Reverse transcription polymerase chain reaction analyses demonstrated expression of TARC in nodular sclerosis (NS) and mixed cellularity (MC) classical Hodgkin's lymphomas but not in NLP Hodgkin's lymphoma, anaplastic large-cell lymphomas, and large-B-cell lymphomas with CD30 positivity. Two of five cases of T-cell-rich B-cell lymphoma (TCRBCL) were TARC positive. RNA in situ hybridization (ISH) showed a strong signal for TARC in the cytoplasm of R-S cells, and immunohistochemical staining confirmed the presence of the TARC protein in the R-S cells of NS and MC Hodgkin's lymphomas. The lymphocytic and histiocytic (L&H)-type cells of nodular lymphocyte predominance Hodgkin's lymphoma and the neoplastic cells of non-Hodgkin's lymphomas with the exception of two cases of TCRBCL did not stain for TARC. TARC is known to bind to the CCR4 receptor, which is expressed on activated Th2 lymphocytes. The immunophenotype of lymphocytes surrounding R-S cells is indeed Th2-like, and by RNA ISH these lymphocytes showed a positive signal for the chemokine receptor CCR4. The findings suggest that production of TARC by the R-S cells may explain the characteristic T-cell infiltrate in classical Hodgkin's lymphoma.
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PMID:High expression of the CC chemokine TARC in Reed-Sternberg cells. A possible explanation for the characteristic T-cell infiltratein Hodgkin's lymphoma. 1036 93

Chemokine receptors mediate the migration of lymphocytes through the binding of ligands, and the expression is differentially regulated in lymphocyte subsets. CXCR3 is usually expressed in Th1 T cells, however, recently is reported to be expressed in B cell chronic lymphocytic leukemia, mucosa-associated lymphoid tissue type lymphoma (MALT) (extranodal marginal zone lymphoma), and other B cell non-Hodgkin lymphomas. Our study was designed to investigate the expression of CXCR3 and its ligand Mig, and their relationships in MALT using immunohistochemistry. In addition, CCR4, which is characteristic Th2 helper phenotype, and its ligand thymus and activation-regulated chemokine (TARC), were compared with CXCR3, as Th1 phenotype. We studied 14 cases of gastric B cell lymphoma [low-grade MALT, 5 cases; high-grade MALT, 5 cases; and diffuse large (DL), 4 cases] and 16 cases of thyroid B cell lymphoma [low-grade MALT, 4 cases; high-grade MALT, 5 cases; and DL, 7 cases]. CXCR3-expressing lymphoid cells were detected in all cases. In double immunostaining (CXCR3-CD20), gastric and thyroid low/high MALT showed CXCR3-positive neoplastic B cells, but DL, except two cases, did not. In DL, CXCR3-positive lymphoid cells were mainly reactive T-cells (CD3-positive cells). Mig was expressed mainly in stromal cells (histiocytes, macrophages, fibroblasts, and endothelial cells). In gastric lymphoma, low-grade MALT contained abundant Mig-strongly expressing cells, while staining in high-grade MALT and DL was mild. In thyroid lymphoma, staining was strong in low- and high-grade MALT, but moderate in DL. In double-staining, CXCR3-Mig-coexpressing lymphoma cells were abundant in high MALT of the stomach and thyroid, but rare in other subtypes. TARC-positive cells and CCR4-positive cells were rarely encountered in all cases. Our results indicate a tendency for low-grade MALT to contain CXCR3(+)Mig- lymphoma cells, high-grade to contain CXCR3(+)Mig+ and DL to contain CRCR3(-)Mig- lymphoma cells. We speculate that CXCR3 is associated with migration of lymphoma cells in low-grade MALT, and autocrine function in high-grade MALT, and not associated with any function in DL.
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PMID:Expression of chemokine receptor CXCR3 and its ligand, mig, in gastric and thyroid marginal zone lymphomas. Possible migration and autocrine mechanism. 1268 53

Leukocyte trafficking is critically regulated by chemokines and their receptors. The involvement of the skin in certain subsets of T-cell malignancies has been explained by the discovery of an interaction between the thymus and activation-regulated chemokine (TARC), which is abundant in the skin, and its receptor, CC chemokine receptor 4 (CCR4), which is expressed in the tumor cells. We describe a diffuse large B-cell lymphoma (DLBCL) that showed CCR4 expression with involvement of the skin. A 55-year-old man presented with a giant skin ulcer of the right axilla, and his disease was diagnosed as DLBCL. Further clinical examination revealed an ulcerated gastric lymphoma lesion. Immunohistochemical and real-time reverse transcriptase-polymerase chain reaction analyses showed that the tumor cells were positive for CCR4, and TARC was expressed at extremely high levels in the lymphoma-affected skin. These observations suggest that the interaction between CCR4 and TARC played a significant role in the involvement of the skin in this case, similar to what has been observed in certain subsets of T-cell malignancies. To the best of our knowledge, this report is the first of a CCR4-positive B-cell lymphoma. The present case provides new insights into the pathogenesis of skin involvement in B-cell lymphomas.
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PMID:CC chemokine receptor 4-positive diffuse large B-cell lymphoma involving the skin: a case report. 1614 48

Age-related Epstein-Barr virus-positive (EBV(+)) B-cell lymphoproliferative disorder (ALPD) is a disease entity identified from a large-scale re-survey of cases diagnosed as diffuse large B-cell lymphoma. ALPD is a group of EBV(+) polymorphic B-cell lymphoma typically seen in elderly patients. An age-associated decline in host immunity against EBV might be partly responsible for the pathogenesis of ALPD. Histologically, ALPD is often characterized by a minor proportion of EBV-encoded RNA-positive tumor cells in a background of extensive cellular infiltration, similar to that of classical Hodgkin's lymphoma. In contrast to Hodgkin and Reed-Sternberg cells, ALPD tumor cells are clearly positive for B cell markers CD20 and/or CD79a. Hodgkin and Reed-Sternberg cells produce various chemokines, including CCL17 and CCL22, that attract chemokine receptor CCR4-expressing Th2 cells and regulatory T cells. Previously, we have shown that EBV-immortalized B cells also produce CCL17 and CCL22 through latent membrane protein 1 (LMP1)-mediated activation of nuclear factor kappaB. Here we examined expression of CCL17 and CCL22 in ALPD. ALPD tumor cells were often heterogeneous in size in accordance with the differential expression of EBV latent genes at the single cell level. LMP1-expressing tumor cells were typically large in size and selectively positive for CCL17 and CCL22. CCR4(+) cells and forkhead box protein 3(+) regulatory T cells were abundantly present, and the majority of forkhead box protein 3(+) cells were CCR4(+). Collectively, our data show production of CCL17 and CCL22 by LMP1(+) large-sized tumor cells and accumulation of CCR4-expressing cells including regulatory T cells in ALPD.
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PMID:Expression of CCL17 and CCL22 by latent membrane protein 1-positive tumor cells in age-related Epstein-Barr virus-associated B-cell lymphoproliferative disorder. 1827 28

Gastric B-cell lymphoma of mucosa-associated lymphoid tissue (MALT) develops in the context of chronic inflammation caused by Helicobacter pylori infection. Most pathophysiological features of the early stages of MALT lymphomagenesis can be reproduced by experimental infection of BALB/c mice with Helicobacter species. We have previously shown that MALT lymphomas are infiltrated by T-helper cell type 2-polarized T cells and that human and murine tumor B cells carry polyreactive surface immunoglobulins. Using the murine model of the disease, in this study we show that explanted tumor B cells proliferate upon stimulation with the same panel of self and foreign antigens that are recognized by their surface antibodies. Tumor cell proliferation is strongly enhanced by the presence of intratumoral CD4(+) T cells in a CD40/CD40L-independent manner. A large proportion of tumor-infiltrating CD4(+) T cells are CD25(+)FoxP3(+) regulatory T cells (Tregs) with highly suppressive activity, which are recruited by the tumor cells through secretion of the Treg-attracting chemokines CCL17 and CCL22. The depletion of CD25(+) cells was as efficient as CD4(+) T cell depletion in blocking tumor growth in vitro and in vivo. In conclusion, our data suggest that B-cell receptor-derived signals cooperate with T-helper cell signals in driving the progression of MALT lymphoma, providing an explanation for the unique antigen dependence of this B-cell malignancy.
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PMID:B-cell receptor signaling and CD40 ligand-independent T cell help cooperate in Helicobacter-induced MALT lymphomagenesis. 2042 2