Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Histone deacetylase (HDAC) inhibitors are promising antitumor agents, but they have not been extensively explored in B-cell lymphomas. Many of these lymphomas have the t(14;18) translocation, which results in increased bcl-2 expression and resistance to apoptosis. In this study, we examined the effects of two structurally different HDAC inhibitors, trichostatin A (TSA) and sodium butyrate (NaB), on the cell cycle, apoptosis, and bcl-2 expression in t(14;18) lymphoma cells. We found that in addition to potent cell cycle arrest, TSA and NaB also dramatically induced apoptosis and down-regulated bcl-2 expression, and overexpression of bcl-2 inhibited TSA-induced apoptosis. The repression of bcl-2 by TSA occurred at the transcriptional level. Western blot analysis and quantitative chromatin immunoprecipitation (ChIP) assay showed that even though HDAC inhibitors increased overall acetylation of histones, localized histone H3 deacetylation occurred at both bcl-2 promoters. TSA treatment increased the acetylation of the transcription factors Sp1 and C/EBPalpha and decreased their binding as well as the binding of CBP and HDAC2 to the bcl-2 promoters. Mutation of Sp1 and C/EBPalpha binding sites reduced the TSA-induced repression of bcl-2 promoter activity. This study provides a mechanistic rationale for the use of HDAC inhibitors in the treatment of human t(14;18) lymphomas.
Mol Cell Biol 2005 Mar
PMID:Histone deacetylase inhibitors down-regulate bcl-2 expression and induce apoptosis in t(14;18) lymphomas. 1571 21

Allicin, a highly active component from freshly crushed garlic, is produced upon the reaction of the small molecular weight molecule alliin, with the enzyme alliinase (EC 4.4.1.4). Because allicin was shown to be toxic to various mammalian cells in vitro, we devised a novel approach for the therapy of B-cell malignancies based on site-directed generation of allicin. Alliinase was conjugated to the monoclonal antibody rituximab, which recognizes the CD20 antigen, and the resulting conjugate was targeted to CD20+ B chronic lymphocytic leukemia (B-CLL) and other B-cell lymphomas. Upon addition of alliin, allicin was formed in situ, killing the CD20+ tumor B cells via apoptosis. Following a 72-hour treatment, an 85% and 96% reduction was observed in the number of viable B-CLL and EBV-transformed B cells, respectively. Using the human/mouse radiation chimera for the evaluation of allicin targeting in a preclinical animal model, we showed a significant reduction in the number of recovered B-CLL, mantle cell lymphoma, or EBV-transformed B cells. We conclude that our system offers a new powerful and less toxic therapy for B-CLL and other B-cell malignancies. Furthermore, combining alliinase with the appropriate monoclonal antibody may extend the application of this approach to other conditions in which the elimination of a specific cell population is desired.
Mol Cancer Ther 2005 Feb
PMID:Apoptotic killing of B-chronic lymphocytic leukemia tumor cells by allicin generated in situ using a rituximab-alliinase conjugate. 1571 3

The translocation t(14;18) resulting in fusion of the BCL2 and the immunoglobulin heavy chain genes (BCL2-IGH) is present in 80% to 90% of follicular lymphomas and 20% to 30% of diffuse large B-cell lymphomas. Polymerase chain reaction (PCR) analysis for the translocation products suffers from low analytic specificity. As a result, either nested PCR or probe hybridization is required to aid in the identification of the specific translocation products. These added procedures are undesirable in clinical laboratories because nested procedures increase the possibility of contamination and probe hybridization increases assay turnaround time. To simplify the BCL2-IGH assay procedure, we attempted to eliminate the nonspecific PCR products by optimizing the annealing temperatures of the PCR assays using a gradient thermocycler. We showed that gradually increasing the annealing temperature from 55 degrees C to 67 degrees C significantly enhanced the intensity of the specific PCR products while eliminating the nonspecific ones. We compared the simplified procedure with a PCR-probe hybridization method on 68 patient specimens. The simplified procedure had increased analytic and diagnostic specificities with comparable sensitivities. With significantly improved analytic specificity, one round of PCR is sufficient to detect the BCL2-IGH gene rearrangements without further confirmation.
Diagn Mol Pathol 2005 Mar
PMID:Detection of BCL2-IGH using single-round PCR assays. 1571 59

The tumor suppressor gene wt1 (Wilms tumor 1) encodes a zinc finger transcription factor reported to be expressed in many tumors, including mesotheliomas, carcinomas, and acute leukemias. However, WT1 expression in non-Hodgkin lymphomas (NHLs) has not been studied. The authors assessed for WT1 expression in six lymphoma/leukemia cell lines using Western blot methods after subcellular fractionation. We also assessed for WT1 expression in 167 NHLs using immunohistochemical methods. The B-cell NHLs analyzed were 18 diffuse large B-cell lymphomas, 13 marginal zone B-cell lymphomas, 9 small lymphocytic lymphomas, (DLBCLs), 8 follicular lymphomas, 6 mantle cell lymphomas, 5 Burkitt lymphomas, 3 lymphoplasmacytic lymphomas, and 2 B-cell lymphoblastic lymphomas. The T-cell NHLs analyzed were 43 anaplastic large cell lymphomas (ALCLs), 26 peripheral T-cell lymphomas unspecified, 13 angioimmunoblastic T-cell lymphomas, 6 cutaneous ALCLs, 6 cases of mycosis fungoides, 5 extranodal NK/T-cell lymphomas of nasal type, and 4 T-cell lymphoblastic lymphomas. WT1 levels were higher in cytoplasmic extracts than in nuclear extracts of the Karpas 299 and SU-DHL-1 lymphoma cell lines but were higher in nuclear extracts than in the cytoplasmic extracts of the Jurkat, HH, U-937, and K562 leukemia cell lines. In NHLs, WT1 was positive in 4 of 5 (80%) Burkitt lymphomas, 9 of 12 (75%) ALK-positive ALCLs, 3 of 6 (50%) lymphoblastic lymphomas (2 of 4 T-cell, 1 of 2 B-cell), 14 of 31 (45%) ALK-negative ALCLs, 6 of 18 (33%) DLBCLs, and 1 of 6 (17%) cutaneous ALCLs. WT1 was negative in all other NHLs tested. WT1 immunoreactivity was primarily cytoplasmic in all positive NHLs except T-cell lymphoblastic lymphoma. In conclusion, WT1 protein is frequently detected in the cytoplasm of a subset of high-grade NHLs.
Appl Immunohistochem Mol Morphol 2005 Jun
PMID:Differential expression of WT1 gene product in non-Hodgkin lymphomas. 1589 24

Expression of CD43 by B cells is often used as a diagnostic criterion in favor of a B-cell lymphoproliferative disorder, including small lymphocytic lymphoma/chronic lymphocytic leukemia, mantle cell lymphoma, Burkitt lymphoma, precursor B-lymphoblastic lymphoma, and a subset of marginal zone B-cell lymphomas. Benign B cells generally do not coexpress CD43. The authors analyzed 20 biopsies of the terminal ileum for nonneoplastic disease for expression of CD43 and compared them with other sites and with CD20, CD138, and CD3 reactivity. The majority of cases (85%) showed strong coexpression of CD43 by benign perifollicular B cells. The presence of CD43 coexpression in B-cell populations of the terminal ileum, including those of Peyer's patches, should not be used as a diagnostic parameter to differentiate extranodal marginal zone B-cell lymphoma of MALT type from reactive processes.
Appl Immunohistochem Mol Morphol 2005 Jun
PMID:Coexpression of CD43 by benign B cells in the terminal ileum. 1589 25

The germinal center plays an important role in the pathogenesis of B-cell lymphomas, and evidence exists to suggest that most cases are germinal center or postgerminal center derived. Burkitt lymphoma and follicular lymphoma are derived from the germinal center stage of differentiation. It has been shown that diffuse large B-cell lymphomas with a germinal center-type pattern of RNA expression or a germinal center cell phenotype using immunocytochemistry have a more favorable outcome compared with those with a postgerminal center/activated profile. Microarray technology may not be available in many diagnostic laboratories, and antibody-based methods are much simpler and cheaper and are therefore more applicable to the routine setting. Immunocytochemistry has the advantage that the cells of interest are identified morphologically, and it is applicable retrospectively to fixed tissue. The main disadvantage is that only single-color staining is currently used in the routine setting. Flow cytometry allows one to obtain a more precise definition of individual cell types. The cells of interest are identified by a combination of physical characteristics and by the use of multiple antibodies labeled with different fluorochromes. Flow cytometry has the major advantage of being able to analyze very large numbers of cells, and results can be obtained within a few hours of the specimen being taken. The methods described allow B-cell lymphomas to be crudely divided into two groups, those with a germinal center phenotype and those that are mainly postgerminal center tumors. As knowledge of the normal biology of the germinal center develops, it will become possible to use immunophenotypic methods to more precisely classify all types of mature B-cell malignancies.
Methods Mol Med 2005
PMID:Demonstration of a germinal center immunophenotype in lymphomas by immunocytochemistry and flow cytometry. 1599 63

Beyond the morphological, immunophenotypic, and genetic information used for the diagnosis of lymphoid malignancies, molecular analyses have deepened our insights into the development of B-cell lymphomas. We have learned that B-cell tumors can be grouped according to the mutational status of their immunoglobulin variable (V) region genes, and this has become an important prognostic tool in chronic lymphocytic leukemia. The analysis of V genes also has allowed us to more precisely place B-cell lymphomas relative to their normal B-cell counterparts and to the germinal center where somatic hypermutation takes place. It has become evident that many of the common B-cell tumors arise at this site and are able to respond to stimuli, which govern normal B-cells. In this chapter, we focus on the analysis of V genes in follicular lymphomas based on the experience in our laboratory and provide a detailed guide for this analysis.
Methods Mol Med 2005
PMID:Idiotype gene rescue in follicular lymphoma. 1599 67

The chromosomal translocation t(9;14)(p13;q32) has been reported in association with lymphoplasmacytic lymphoma (LPL). Although this translocation involving the paired homeobox-5 (PAX5) gene at chromosome band 9p13 and the immunoglobulin heavy chain (IgH) gene at 14q32 has been described in approximately 50% of LPL cases, the actual number of cases studied is quite small. Many of the initial cases associated with t(9;14)(p13;q32) were actually low-grade B-cell lymphomas with plasmacytic differentiation other than LPL. Thus, we analyzed a series of low-grade B-cell lymphomas for PAX5 gene rearrangements. We searched records from the Department of Pathology, Stanford University Medical Center for low-grade B-cell lymphomas, with an emphasis on plasmacytic differentiation, that had available paraffin blocks or frozen tissue. We identified 37 cases, including 13 LPL, 18 marginal zone lymphomas (nodal, extranodal, splenic, and alpha-heavy chain disease), and 6 small lymphocytic lymphomas. A novel dual-color break-apart bacterial artificial chromosome probe was designed to flank the PAX5 gene, spanning previously described PAX5 breakpoints, and samples were analyzed by interphase fluorescence in situ hybridization. All cases failed to demonstrate a PAX5 translocation, indicating that t(9;14)(p13;q32) and other PAX5 translocations are uncommon events in low-grade B-cell lymphomas with plasmacytic differentiation. This study also confirms recent reports that found an absence of PAX5 rearrangements in LPL, suggesting the reassessment of PAX5 rearrangements in LPL.
J Mol Diagn 2005 Aug
PMID:Low-grade B-Cell lymphomas with plasmacytic differentiation lack PAX5 gene rearrangements. 1604 6

Chromosomal translocations juxtaposing different oncogenes to the immunoglobulin (IG) loci are the hallmark of various B-cell lymphomas. Because the tumor cells in nodular lymphocyte predominant Hodgkin's lymphoma (NLPHL) are also derived from B cells, we examined whether NLPHL harbors chromosomal translocations that affect IG loci. Fluorescence in situ hybridization was applied to 24 NLPHL cases using probes flanking the IGH, IGK, and IGL loci as well as the BCL6 gene. Fourteen of these cases were additionally analyzed by combined immunofluorescence and fluorescence in situ hybridization. Chromosomal breakpoints in the IGH locus were detected in five NLPHL. All these cases also contained a BCL6 breakpoint. Triple-color interphase cytogenetics demonstrated the presence of an IGH-BCL6 juxtaposition, indicating a t(3;14)(q27;q32) in all five cases. There was no evidence for breakpoints affecting the IGK or IGL loci. Our results show that translocations juxtaposing the BCL6 oncogene next to the IGH locus are recurrent in NLPHL.
J Mol Diagn 2005 Aug
PMID:Molecular cytogenetic analyses of immunoglobulin loci in nodular lymphocyte predominant Hodgkin's lymphoma reveal a recurrent IGH-BCL6 juxtaposition. 1604 7

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


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>