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Query: UMLS:C0079731 (B-cell lymphoma)
 16,671 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

CH12 is a murine B-cell lymphoma whose surface immunoglobulin (sIg) and concanavalin A (Con A) receptors patch and cap readily. Actin may be involved in CH12 patching and capping, since fodrin and F-actin collect under the cap, and cytochalasin D inhibits sIg capping. We have examined the state of the actin cytoskeleton during patching and capping. A wide range of concentrations of rabbit anti-mouse antibody (RAM) and Con A were used to patch or cap CH12 cells. G-actin was quantitated by DNase I inhibition, F-actin was quantitated by fluorescence-activated cell sorter analysis of fluorescent phalloidin staining, and actin nucleation sites were measured by pyrene actin polymerization. None of these methods detected any significant changes in actin when compared to control cells or untreated cells, leading us to conclude that increased actin polymerization is not necessary for capping to occur. The significance of these data to the membrane flow and cytoskeletal models of capping is discussed.
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PMID:Polymerization of additional actin is not required for capping of surface antigens in B-lymphocytes. 278 5

A new promoter of the human c-myc gene called P0, with multiple RNA start sites, was mapped over 500 bases upstream of the two previously identified promoters, P1 and P2. Sequencing full-length cDNA clones of P0 RNAs revealed two open reading frames upstream of that for the P64c-myc protein. P0 RNA is located on polyribosomes and released by puromycin, indicating that it functions as an mRNA. In vitro translation of RNA synthesized from the cloned cDNAs predicts that P0 transcripts are translated into a novel 12.5-kilodalton protein corresponding to the first open reading frame. The regulation of P0 RNA was studied in the B-cell lymphoma cell line Manca, in which only the translocated c-myc allele lacking exon 1 was thought to be active. However, we found that P0 transcription and the DNase I-hypersensitive site associated with this promoter persist on the untranslocated allele, even though P1/P2 transcription as measured by a nuclear runoff assay was repressed. These results suggest that allelic exclusion of c-myc expression in this B-cell lymphoma is caused by a repression of transcription which is specific to the P1/P2 promoters. We previously reported a block to elongation of transcription near the 3' end of exon 1 in the wild-type c-myc gene, which results in an excess of exon 1 over exon 2 transcription (5a). In contrast, we found that in the Daudi B-cell lymphoma, which retains exon 1 in the active allele, equimolar transcription of exons 1 and 2 occurs. This result suggests a model for the activation of c-myc in B-cell lymphomas.
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PMID:Novel promoter upstream of the human c-myc gene and regulation of c-myc expression in B-cell lymphomas. 354 May 91

Transcription of unrearranged kappa constant region (kappa 0) loci is dramatically induced in pre-B cells transformed by the Abelson murine leukemia virus when the cells are exposed to bacterial lipopolysaccharide (LPS). Transcriptional activity, detected both by accumulation of the 8-kilobase kappa 0 RNA product and by nuclear run-on measurements, is evident within a few hours after exposure to LPS and continues to increase over a 24-hr period. During this time, transcription of rearranged mu heavy-chain loci remains at the basal constitutive level. In accord with previous studies of the B-cell lymphoma 70Z/3, this transcriptional activation is accompanied by the appearance of a DNase I-hypersensitive site in the kappa enhancer region but not by any detectable hypomethylation of the locus. Moreover, the present studies demonstrate that induction of kappa transcription can occur in the absence of DNA or protein synthesis. These results have led us to propose a model in which an external signal such as LPS or a functionally equivalent lymphokine may initiate kappa transcription in pre-B cells by modifying or overriding the activity of an enhancer-specific factor.
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PMID:Inducible transcription of the unrearranged kappa constant region locus is a common feature of pre-B cells and does not require DNA or protein synthesis. 392 1

The rearrangement of a variable (V) and a constant (C) gene appears to be a necessary prerequisite for immunoglobulin gene expression. Multiple different rearranged kappa genes were found in several mouse myelomas, although these cells produce only one type of kappa chain [Wilson, R., Miller, J., & Storb, U. (1979) Biochemistry 18, 5013--5021]. It is therefore of interest to understand how only one allele within a lymphoid cell becomes expressed, while the other allele remains nonfunctional ("allelic exclusion"). We have studied the chromatin conformation of kappa genes by making use of the preferential digestion of potentially active genes by DNase I described, for example, for globin genes [Weintraub, H., & Groudine, M. (1976) Science (Washington, D.C.) 193, 848--856]. The DNase I sensitivity of kappa genes in myeloma tumors, in a B cell lymphoma, and in liver was determined by hybridization with DNA on Southern blots. It was found that rearranged C kappa genes are DNase I sensitive in myelomas in which several kappa genes are rearranged, regardless of whether the rearranged genes code for the kappa chains synthesized by the cell. Furthermore, the C kappa gene in germline configuration is also DNase I sensitive in a B cell lymphoma; i.e., it is in the same chromatin state as the rearranged C kappa gene which probably codes for the kappa chains produced by the cell. The altered chromatin state appears to be localized: V kappa genes in germline context are not DNase I sensitive in myeloma or B lymphoma cells while C kappa genes present in a kappa gene cluster on the same chromosomes are sensitive. When rearranged, however, the V kappa genes are as sensitive to DNase I as are rearranged C kappa genes. V lambda and C lambda genes are not DNase I sensitive in kappa myelomas. Thus, commitment to kappa gene expression is apparently correlated with a chromatin conformation which confers increased DNase I sensitivity to the DNA in the vicinity of all C kappa genes in the cell. "Allelic exclusion" does not operate on the level of chromatin conformation which can be detected by altered DNase I sensitivity.
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PMID:Rearranged and germline immunoglobulin kappa genes: different states of DNase I sensitivity of constant kappa genes in immunocompetent and nonimmune cells. 626 Jan 46

The cyclin D1/bcl-1 proto-oncogene is one of a series of genes encoding proteins which regulate the cell cycle and are involved in the multistep process of tumorigenesis. Translocation of the cyclin D1 proto-oncogene is a common event in B cell lymphoma, and cyclin D1 amplification occurs in breast, esophageal, hepatocellular, and head/neck carcinomas. The human cyclin D1 proto-oncogene promoter contains an 18-base pair purine-pyrimidine rich motif with three C.G interruptions. This motif is a potential target for purine.purine. pyrimidine triplex formation. We have designed a G-rich antiparallel triplex forming oligonucleotide (TFO) targeted to this region. Electrophoretic mobility shift analysis (EMSA) shows that this purine-pyrimidine rich motif is a binding site for the transcription factor Sp1 and that triplex formation by the target sequence prevents the binding of recombinant Sp1. The exact location of triplex formation was confirmed by DNase I footprinting. In an attempt to increase stability, we have used modified phosphorothioate oligonucleotides for cell culture experiments. Triplex formation by the cyclin D1 targeted phosphorothioate oligonucleotide occurs with a binding affinity approximately equal to that of phosphodiester oligonucleotides. This phosphorothioate modified TFO targeted to cyclin D1 also inhibits transcription of the cyclin D1 promoter in HeLa cells, as demonstrated by a decrease in luciferase expression from a stably integrated human cyclin D1 promoter driven luciferase construct. This suggests that triplex formation may represent a gene specific means of inhibiting cyclin D1 expression.
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PMID:A novel triplex-forming oligonucleotide targeted to human cyclin D1 (bcl-1, proto-oncogene) promoter inhibits transcription in HeLa cells. 948 17

In B cells, the Igh gene locus contains several DNase I-hypersensitive (hs) sites with enhancer activity. These include the 3' Igh enhancers, which are located downstream of the Calpha gene(s) in both mouse and human. In vivo experiments have implicated murine 3' enhancers, hs3B and/or hs4, in class switching and somatic hypermutation. We previously reported that murine hs4 was regulated by NF-kappaB, octamer binding proteins, and Pax5 (B cell-specific activator protein). In this study we report that human hs4 is regulated differently. EMSAs and Western analysis of normal B cells before and after stimulation with anti-IgM plus anti-CD40 showed the same complex binding pattern formed by NF-kappaB, Oct-1, and Oct-2 (but not by Pax5). A similar EMSA pattern was detected in mature human B cell lines (BL-2, Ramos, and HS-Sultan) and in diffuse large B cell lymphoma cell lines, although yin yang 1 protein (YY1) binding was also observed. We have confirmed the in vivo association of these transcription factors with hs4 in B cells by chromatin immunoprecipitation assays. The diffuse large B cell lymphoma cell lines had a distinctive slow-migrating complex containing YY1 associated with Rel-B. We have confirmed by endogenous coimmunoprecipitation an association of YY1 with Rel-B, but not with other NF-kappaB family members. Transient transfection assays showed robust hs4 enhancer activity in the mature B cell lines, which was dependent on synergistic interactions between NF-kappaB and octamer binding proteins. In addition, human hs4 enhancer activity required Oct-2 and correlated with expression of Oct coactivator from B cells (OCA-B).
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PMID:NF-kappa B and Oct-2 synergize to activate the human 3' Igh hs4 enhancer in B cells. 1470 79

Burkitt's lymphoma is invariably associated with chromosomal translocations that juxtapose the c-myc proto-oncogene with regulatory elements of the immunoglobulin heavy (IgH) or light chain loci resulting in the deregulation of c-myc expression. However, the enhancer elements mediating c-myc deregulation in vivo remain largely unidentified. To investigate the role of the IgH 3'-enhancers in c-myc deregulation, we used gene targeting to generate knock-in mice in which four DNase I hypersensitive regions from the murine IgH 3'-region were integrated into the 5'-region of the c-myc locus. The IgH 3'-enhancers induced the up-regulation of c-myc expression specifically in B cells of IgH-3'-E-myc mice. After approximately 10 months, the mice developed a Burkitt-like B cell lymphoma with the phenotype of B220+, IgM+, and IgD(low). Analysis of immunoglobulin gene rearrangements indicated that the lymphoma cells were of clonal origin. The presence of a rapidly expanding population of B cells in the spleen and bone marrow of young knock-in mice at 2-4 months of age was observed. Premalignant splenic B cells of knock-in mice showed higher spontaneous and induced apoptosis; however, malignant B cells were more resistant to apoptosis. The p53-ARF-Mdm2 pathway was disabled in half of the lymphomas examined, in most cases through Mdm2 overexpression. Although c-myc expression was increased in premalignant B cells, the promoter shift from P2 to P1 was observed only in malignant B cells. Our studies demonstrate that the IgH 3'-enhancers play an important role in c-myc deregulation and B cell lymphomagenesis in vivo.
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PMID:Regulatory elements in the immunoglobulin heavy chain gene 3'-enhancers induce c-myc deregulation and lymphomagenesis in murine B cells. 1568 98

SYNOPSIS: Reports that elasmobranchs (sharks, skates, and rays) may have a low incidence of disease have stimulated interest in understanding the role of their immune system in this apparent resistance. Although research in this area may potentially translate into applications for human health, a basic understanding of the elasmobranch immune system components and how they function is essential. As in higher vertebrates, elasmobranch fishes possess thymus and spleen, but in the absence of bone marrow and lymph nodes, these fish have evolved unique lymphomyeloid tissues, namely epigonal and Leydig organs. As conditions for short-term culture of elasmobranch immune cells have become better understood, the opportunity to examine functional activity of cytokine-like factors derived from conditioned culture medium has resulted in the identification of growth inhibitory activity against a variety of tumor cell lines. Specifically, the medium enriched by short term culture of bonnethead shark (Sphyrna tiburo) epigonal cells (epigonal conditioned medium, ECM) has been shown to inhibit the growth of mammalian tumor cell lines, including fibrosarcoma (WEHI-164), melanoma (A375.S2), B-cell lymphoma (Daudi), T-cell leukemia (Jurkat), pancreatic cancer (PANC-1), ovarian cancer (NIH:OVCAR-3), and three breast carcinoma cell lines (MCF7, HCC38, Hs578T). Of the cell lines tested, WEHI-164, A375.S2, Daudi, and Jurkat cells were among the most sensitive to growth inhibitory activity of ECM whereas PANC-1 and NIH:OVCAR-3 cells were among the least sensitive. In addition, ECM demonstrated preferential growth inhibition of malignant cells in assays against two different malignant/non-malignant cell line pairs (HCC38/HCC38 BL and Hs 578T/Hs 578Bst). Separation of protein components of ECM using SDS-PAGE resulted in a very reproducible pattern of three major bands corresponding to molecular sizes of approximately 40-42 kD, 24 kD, and 17 kD. Activity is lost after heating at 75 degrees C for 30 min, and can be diminished by treatment with proteinase K and protease. Activity is not affected by treating with trypsin, DNase I or RNase A.
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PMID:Elasmobranch immune cells as a source of novel tumor cell inhibitors: Implications for public health. 1934 8

BCL6 is essential for normal antibody responses and is highly expressed in germinal centre B-cells. Constitutive expression due to chromosomal translocations or mutations of cis-acting regulatory elements contributes to diffuse large B-cell lymphoma. BCL6 expression is therefore tightly regulated in a lineage- and developmental-stage-specific manner, and disruption of normal controls can contribute to lymphomagenesis. In order to discover potential cis-acting control regions we carried out DNase I-hypersensitive site mapping. Gel-shift assays and chromatin immunoprecipitation of the core region of a hypersensitive site 4.4 kb upstream of BCL6 transcription initiation (HSS-4.4) showed an E-box element-binding ZEB1 (zinc finger E-boxbinding homeobox 1) and the co-repressor CtBP (C-terminal binding protein). As compared with peripheral blood B-cells, ZEB1, a two-handed zinc finger transcriptional repressor, is expressed at relatively low levels in germinal centre cells, whereas BCL6 has the opposite pattern of expression. Transfection of ZEB1 cDNA caused a reduction in BCL6 expression and a mutated ZEB1, incapable of binding CtBP, lacked this effect. siRNA (small interfering RNA)-mediated knockdown of ZEB1 or CtBP produced an increase in BCL6 mRNA. We propose that HSS-4.4 is a distal promoter element binding a repressive complex consisting of ZEB1 and CtBP. CtBP is ubiquitously expressed and the results of the present study suggest that regulation of ZEB1 is required for control of BCL6 expression.
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PMID:ZEB1 and CtBP form a repressive complex at a distal promoter element of the BCL6 locus. 2017 52

The nuclear factor of activated T cells (NFAT) family of transcription factors functions as integrators of multiple signaling pathways by binding to chromatin in combination with other transcription factors and coactivators to regulate genes central for cell growth and survival in hematopoietic cells. Recent experimental evidence has implicated the calcineurin/NFAT signaling pathway in the pathogenesis of various malignancies, including diffuse large B-cell lymphoma (DLBCL). However, the molecular mechanism(s) underlying NFATc1 regulation of genes controlling lymphoma cell growth and survival is still unclear. In this study, we demonstrate that the transcription factor NFATc1 regulates gene expression in DLBCL cells through a chromatin remodeling mechanism that involves recruitment of the SWItch/Sucrose NonFermentable chromatin remodeling complex ATPase enzyme SMARCA4 (also known as Brahma-related gene 1) to NFATc1 targeted gene promoters. The NFATc1/Brahma-related gene 1 complex induces promoter DNase I hypersensitive sites and recruits other transcription factors to the active chromatin site to regulate gene transcription. Targeting NFATc1 with specific small hairpin RNA inhibits DNase I hypersensitive site formation and down-regulates target gene expression. Our data support a novel epigenetic control mechanism for the transcriptional regulation of growth and survival genes by NFATc1 in the pathophysiology of DLBCL and suggests that targeting NFATc1 could potentially have therapeutic value.
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PMID:An epigenetic chromatin remodeling role for NFATc1 in transcriptional regulation of growth and survival genes in diffuse large B-cell lymphomas. 2066 54


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