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

The p63 gene, a homolog of the tumor suppressor gene TP53, maps to chromosome 3q27-28, a region frequently displaying genomic amplification in squamous cell carcinomas. p63 is expressed in a variety of epithelial tissues and has been reported to be critical for the normal development of stratified epithelia, including skin epidermis. In a previous study, the authors reported the expression of p63 in occasional cells in the germinal center of lymph nodes and also observed p63 expression in B-cell lymphomas, among other tumor types surveyed in that analysis. The present study was conducted to further analyze the potential clinical significance of identifying p63 expression, assessing a larger cohort of well-characterized patients with diffuse large B-cell lymphoma (DLBCL) (n = 172 cases) and a panel of established lymphoma cell lines. p63 expression at the microanatomic detail was examined by immunohistochemistry using a monoclonal antibody (clone 4A4), while distinction of p63 isoforms was analyzed by Western blotting and reverse transcription-polymerase chain reaction using isoform-specific primers. The authors found that a subset of DLBCL (32% of cases) expressed p63 in the nuclei of neoplastic lymphocytes. Examination of the different p63 isoforms revealed that the DeltaNp63 species was expressed by only one cell line, while the other p63 isoforms were found in most cell lines analyzed. The authors also observed that p63 expression correlated with high proliferative index, as assessed by Ki-67 immunostaining. Even though in univariate analysis p63 expression did not correlate with overall survival, the association of p63 with increased proliferative index suggests its involvement in DLBCL tumor progression.
Appl Immunohistochem Mol Morphol 2005 Sep
PMID:Expression of p63 in diffuse large B-cell lymphoma. 1608 48

B-cell lymphoma 6 (BCL6) is a 95-kDa nuclear phosphoprotein and member of the Pox virus zinc finger/bric-a-brac, tramtrack, broad complex (POZ/BTB) family of transcription factors. BCL6 is a transcriptional repressor required for germinal center formation, and the gene encoding it is frequently altered in diffuse large B-cell and follicular lymphomas. The dysregulation of BCL6 has therefore been implicated in lymphomagenesis. A limited number of proteins is known to interact with BCL6 and modulate its activity or participate in its role in transcriptional regulation. Identification of additional BCL6-binding proteins could reveal potential signaling targets and previously undescribed functional roles for BCL6. We used a functional proteomic approach to determine the identity of proteins that interact with BCL6. Proteins were isolated by co-immunoprecipitation with an anti-BCL6 antibody and identified using MS/MS. We identified 61 proteins in the BCL6 immunocomplex from the following Gene Ontology categories: transcription regulator activity (n = 18), binding activity (n = 11), signal transducer activity (n = 10), catalytic activity (n = 8), structural molecule activity (n = 3), enzyme regulator activity (n = 3), transporter activity (n = 2), motor activity (n = 2), chaperone activity (n = 1), and unknown function (n = 3). Importantly we identified BCL6 and several previously reported BCL6-interacting proteins in the BCL6 immunocomplex. The remaining proteins have not been shown previously to be associated with BCL6. MS/MS results were validated on four proteins using immunoprecipitation and Western blotting. Two of these protein interactions were further confirmed by reciprocal immunoprecipitation. This study demonstrates the utility of antibody immunoprecipitation and subsequent peptide identification by MS/MS for the elucidation of BCL6-binding proteins. Many of the novel proteins identified in this study suggest additional functional roles for BCL6 beyond transcriptional repression.
Mol Cell Proteomics 2005 Dec
PMID:Analysis of BCL6-interacting proteins by tandem mass spectrometry. 1614 92

This study aims to assess the distribution of lymphoma subtypes in Shanxi, China, according to the World Health Organization (WHO) classification, and to compare the relative distribution with other areas of the world. H&E-stained tissue sections from the archives of the Shanxi Tumor Hospital, China, were reviewed and 447 cases with sufficient materials were selected for detailed study. A panel of antibodies and probes was assembled, including antibodies to ALK1, bcl-6, CDs 1alpha, 3, 4, 5, 7, 8, 10, 15, 20, 23, 30, 43, 56, 68, 79alpha, and 99, cyclin D1, EMA, kappa, lambda, LMP1, PAX5, TdT, Vs38C and ZAP70, plus EBER RNA probe by in situ hybridization. The 447 lymphoma cases, subtyped according to the WHO classification, were assembled in triplicate into 11 tissue microarrays and examined with the panel of markers described. Among the 447 cases, 385 (82.6%) were confirmed to be non-Hodgkin lymphomas (NHL) and 62 (13.9%) were Hodgkin lymphomas of classic type (CHL). Of the NHL cases, 68.6% were B-cell lymphomas and 30.6% T/NK-cell lymphomas. Histiocytic neoplasms accounted for only three cases (0.8%). Diffuse large B-cell lymphomas (DLBCL) were the most common subtype (35.1%), followed by peripheral T-cell lymphomas unspecified (PTun, 12.0%), extranodal marginal zone B-cell lymphomas (MALT lymphomas, 11.7%), follicular lymphomas (FL, 8.6%), T-lymphoblastic lymphomas (T-LBL, 7.0%), anaplastic large cell lymphomas (ALCL, 4.2%), B small lymphocytic lymphomas (B SLL, 3.6%), and mantle cell lymphomas (MCL, 2.6%). Of 263 B-cell neoplasms, 105 (39.9%) expressed immunoglobulin light chain, including 52 kappa and 53 lambda, detectable in paraffin sections. The incidence of DLBCL was similar to many Western countries and Asia. The frequency of FL was, however, much lower than the usual pattern in Western countries, although NK/T-cell lymphomas were more common (30.6%), similar to other countries in Asia, including Japan and Korea. With regard to markers of EBV infection, 8 of 385 (2.1%) NHL cases gave positive findings by both in situ hybridization (EBER RNA) and immunohistochemistry (LMP-1), whereas 24 (6.2%) expressed only the EBER and 12 (3.1%) expressed only LMP-1. EBV positivity was found in 24 of 119 (20.2%) T and NK cell lymphomas, in 20 of 263 (7.6%) B cell neoplasms, and in 37 of 62 (59.7%) CHLs. In CHLs there was complete concordance of results by both in situ hybridization (EBER RNA) and immunohistochemistry (LMP-1) procedures. ZAP70 was detected in most T cell-lineage disorders (61.4%) and also in a subset of B small lymphocytic lymphomas (50%). However, ZAP-70 was expressed in a minority of other types of B-cell lymphomas, including precursor B-cell acute lymphoblastic leukemia (25%), diffuse large B-cell lymphoma (26.7%), follicular lymphoma (15.2%), and lymphoplasmacytic lymphoma (9.1%). Immunohistochemical analysis represents an effective method for assessing ZAP-70 expression and reveals that a variety of B-cell malignant neoplasms express ZAP-70, albeit at low frequency.
Appl Immunohistochem Mol Morphol 2005 Dec
PMID:Distribution and ZAP-70 expression of WHO lymphoma categories in Shanxi, China: a review of 447 cases using a tissue microarray technique. 1628 Jun 61

To glean biological differences and similarities of peripheral T-cell lymphoma-not otherwise specified [PTCL-NOS] to diffuse large B-cell lymphoma (DLBCL), a transcriptosome analysis was done on five PTCL-NOS and four DLBCL patients and validated by quantitative real-time reverse transcription-PCR on 10 selected genes. Normal peripheral blood T cells, peripheral blood B cells, and lymph node were used as controls. The resultant gene expression profile delineated distinct "tumor profile signatures" for PTCL-NOS and DLBCL. Several highly overexpressed genes in both PTCL-NOS and DLBCL involve the immune network, stroma, angiogenesis, and cell survival cascades that make important contributions to lymphomagenesis. Inflammatory chemokines and their receptors likely play a central role in these complex interrelated pathways: CCL2 and CXCR4 in PTCL-NOS and CCL5 and CCR1 in DLBCL. Highly overexpressed oncogenes unique to PTCL-NOS are SPI1, STK6, alpha-PDGFR, and SH2D1A, whereas in DLBCL they are PIM1, PIM2, LYN, BCL2A1, and RAB13. Oncogenes common to both lymphomas are MAFB, MET, NF-kappaB2, LCK, and LYN. Several tumor suppressors are also down-regulated (TPTE, MGC154, PTCH, ST5, and SUI1). This study illustrates the relevance of tumor-stroma immune trafficking and identified potential novel prognostic markers and targets for therapeutic intervention.
Mol Cancer Ther 2005 Dec
PMID:Transcript profiling in peripheral T-cell lymphoma, not otherwise specified, and diffuse large B-cell lymphoma identifies distinct tumor profile signatures. 1637 2

Naked DNA vaccines have a number of advantages over conventional vaccines, but induce only weak immune responses. We have here investigated if this inadequacy may be overcome by inducing muscle to secrete fusion proteins with the ability to target antigen-presenting cells (APC). The novel targeted vaccines are homodimers with (i) two identical single-chain fragment variable (scFv) targeting units specific for MHC class II molecules on mouse APC, (ii) a human Ig hinge and C(H)3 dimerization unit, and (iii) two identical scFv tumor antigenic units (idiotypes) from B cell cancers. After plasmid injection and electroporation of mouse muscle, secreted vaccine proteins (vaccibodies) delivered idiotypic tumor antigen to APC in draining lymph nodes for induction of T and B cell responses that protected mice against tumor challenges with a multiple myeloma (MOPC315) and a B cell lymphoma (A20). Targeting to APC was essential for these effects. The results show that immunogenicity of plasmid DNA vaccines can be increased by inducing muscle to secrete proteins that target antigen to APC.
Mol Ther 2006 Apr
PMID:DNA vaccines increase immunogenicity of idiotypic tumor antigen by targeting novel fusion proteins to antigen-presenting cells. 1641 9

Micromet AG and Medlmmune Inc are developing MT-103, a single-chain bispecific recombinant antibody from Micromet's BiTE (bispecific T-cell engager) product platform that binds both the CD19 antigen and the T-cell receptor (CD3), for the potential treatment of B-cell lymphoma. The company is also investigating the compound for the potential treatment of chronic lymphocytic leukemia and acute lymphoblastic leukemia.
Curr Opin Mol Ther 2006 Feb
PMID:MT-103 Micromet/MedImmune. 1650 27

Overexpression of transferrin receptor 1 (TFRC1), a major mediator of iron uptake in mammalian cells, is a common feature of human malignancies. Therapeutic strategies designed to interfere with tumor iron metabolism have targeted TFRC1. The c-Myc oncogenic transcription factor stimulates proliferation and growth by activating thousands of target genes. Here we demonstrate that TFRC1 is a critical downstream target of c-Myc. Using in vitro and in vivo models of B-cell lymphoma, we show that TFRC1 expression is activated by c-Myc. Chromatin immunoprecipitation experiments reveal that c-Myc directly binds a conserved region of TFRC1. In light of these findings, we sought to determine whether TFRC1 is required for c-Myc-mediated cellular proliferation and cell size control. TFRC1 inhibition decreases cellular proliferation and results in G1 arrest without affecting cell size. Consistent with these findings, expression profiling reveals that TFRC1 depletion alters expression of genes that regulate the cell cycle. Furthermore, enforced TFRC1 expression confers a growth advantage to cells and significantly enhances the rate of c-Myc-mediated tumor formation in vivo. These findings provide a molecular basis for increased TFRC1 expression in human tumors, illuminate the role of TFRC1 in the c-Myc target gene network, and support strategies that target TFRC1 for cancer therapy.
Mol Cell Biol 2006 Mar
PMID:Activation of transferrin receptor 1 by c-Myc enhances cellular proliferation and tumorigenesis. 1650 12

Although the small B-cell lymphomas show major morphologic overlapping, they have been recently shown to be distinct entities with several biologic and clinical differences. Therefore, the utility of a panel of paraffin-reactive antibodies in differentiating these neoplasms was investigated. Using clinical data and morphologic criteria, 134 cases of small B-cell lymphomas were grouped as those with (1) one strongly suggested diagnosis, (2) differential diagnosis between two types of lymphomas, and (3) small B-cell lymphoma without hints for further subclassification. With a panel of antibodies including CD5, CD10, CD23, CD43, bcl-2, and cyclin D1, most but not all cases could be precisely categorized. This panel confirmed the diagnosis in 96.5% of the cases from group 1. In group 2 it confirmed one of the two diagnoses in 81.5% of the cases. In group 3 it established a definitive diagnosis in 55% of the cases. When all groups were considered, a correct diagnosis could be established for 88.1% of cases; for 6.7% of them the authors remained with two possible diagnosis, and the broad "small B-cell lymphoma" was the only diagnosis for 5.2% of cases. CD10 separated most follicular lymphomas from other small B-cell lymphoid neoplasms. CD23 separated small lymphocytic lymphoma/chronic lymphocytic leukemia. Cyclin D1 separated mantle cell lymphoma. The present study selected CD10, CD23, and cyclin D1 as a minimal panel for the classification of small B-cell lymphomas, yielding a final diagnosis in 88.1% of the cases.
Appl Immunohistochem Mol Morphol 2006 Mar
PMID:Contribution of immunohistochemistry to small B-cell lymphoma classification. 1654 Jul 22

In this article, we show how to apply our previously proposed Deletion/Substitution/Addition algorithm in the context of right-censoring for the prediction of survival. Furthermore, we introduce how to incorporate bagging into the algorithm to obtain a cross-validated bagged estimator. The method is used for predicting the survival time of patients with diffuse large B-cell lymphoma based on gene expression variables.
Stat Appl Genet Mol Biol 2006
PMID:Cross-validated bagged prediction of survival. 1667 66

The expression of RAG1 and RAG2 is essential for V(D)J rearrangement of the immunoglobulin (Ig) locus in developing B cells. In mature B cells further V(D)J rearrangement is suppressed and RAG1/2 proteins decline to undetectable levels. However, there is evidence that mature B cells in the periphery may re-express RAG1/2. In humans evidence of RAG1/2 re-expression is often linked with an autoimmune state, indicating that further understanding of re-expression may be crucial to understanding immune disorders. We have investigated the molecular consequences of RAG1/2 expression in mature lymphocytes using a cell culture system (M12 and DR3). M12 (IgG+, Igkappa+ and RAG-) is a mouse B cell lymphoma. DR3 is a RAG1+/RAG2+ line derived from M12 by introduction of stable plasmids carrying RAG1 and RAG2 cDNAs. RAG1/2 mediated receptor revision occurs in the DR3 line, as evidenced by both the deletion of the endogenous rearranged Igkappa gene segment (present in the parent M12 lines) and the presence of a new Iglambda rearrangement. Gene expression profiles obtained through microarray analysis and RT-PCR found differences in expression levels between the two lines for: fibronectin, lysyl oxidase, TAP2, B220, Igkappa, TIS11B, HMG2 and DNAPKcs. Thus, the expression of RAG1/2 in a previously RAG- cell line results in multiple changes to the gene expression profile as well as receptor revision. The significance of the changes found in this model of RAG re-expression is discussed.
Mol Immunol 2007 Feb
PMID:RAG1/2 re-expression causes receptor revision in a model B cell line. 1670 98


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