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)

B-cell lymphoma, which is increasing world wide, includes such varied conditions as post-transplant lymphoproliferative disease (PTLD) and Burkitt's lymphoma. This study has characterized a role for the signalling molecule phosphatidylinositol 3-kinase, PI3K, in the regulation of growth and survival of immortalized B-lymphocytes. Burkitt's lymphoma cells die rapidly following inhibition of PI3K with LY294002, a chemical inhibitor. Furthermore, Epstein-Barr virus (EBV) immortalized B-cells, lymphoblastoid cell lines, which are a model of PTLD, do not die but are growth inhibited. This growth inhibition is due to an accumulation at G1 phase of the cell cycle and is paralleled by a loss of E2F transcriptional activity, which is essential for cell cycle entry. An active form of PI3K promotes E2F transcriptional activity in lymphoblastoid cell lines. Treatment of LCL with LY294002 causes a reduction of the expression of both cyclin D2 and cyclin D3, two key cyclins required for cell cycle progression but does not affect the expression of the EBV latent genes, EBNA2A or LMP-1. LY294002 also causes an increase in p27kip1, a cyclin dependent kinase inhibitor and results in the dephosphorylation of members of the pocket protein family. These data describe a mechanism by which PI3K plays a role in B-lymphocyte growth and suggests that a pathway from PI3K to D-type cyclin expression may provide diagnostic or treatment opportunities.
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PMID:Phosphatidylinositol 3-kinase is essential for the proliferation of lymphoblastoid cells. 1185 Aug 46

Chromosomal rearrangements in non-Hodgkin's B-cell lymphoma implicate BCL-6 as an oncogene, yet direct evidence for BCL-6 acting as an oncogene in B cells has been lacking. Here, we show that BCL-6 can immortalize primary B cells, but only in the absence of p53 tumor suppressor function. The expression of BCL-6 led to greatly increased B-cell proliferation, particularly in response to CD40 stimulation. Furthermore, BCL-6-infected p53-deficient B cells gave rise to immortalized cell lines that could be maintained by CD40 stimulation. We found that in primary mouse B cells, BCL-6 repressed expression of the Blimp-1, p27kip1, and cyclin D2 target genes. BCL-6 did not markedly repress the PDCD2 and BCL-XL target genes. The BCL-6 immortalized cell lines had a phenotype consistent with germinal center B cells, they expressed the germinal center-specific M17 gene, and a significant fraction of the cells stained positive with PNA. Our data indicate that BCL-6 may act to maintain B cells in a germinal center-like state, and repression of Blimp-1 by BCL-6 may be particularly crucial for stabilization of the germinal center phenotype. Our data also suggest that disruption of the p53 pathway may be crucial for the development of BCL-6-expressing B-cell lymphomas.
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PMID:Transcriptional repressor BCL-6 immortalizes germinal center-like B cells in the absence of p53 function. 1473 19

Cyclin-dependent protein kinase 6 (CDK6), in cooperation with cyclin Ds, drives cell cycle progression from G1 to S phase through phosphorylation and subsequent inactivation of retinoblastoma 1 protein. Alteration of this pathway results in both nonhematologic and hematologic malignancies, which include a small subset of B-cell lymphoproliferative disorders (BLPDs). We identified 5 cases of BLPD that carried CDK6 chromosomal translocations and characterized their clinical, pathologic, immunophenotypic, and genetic features. Common clinical characteristics included marked neoplastic lymphocytosis, systemic lymphadenopathy, splenomegaly, and bone marrow involvement. Three patients were diagnosed with low-grade B-cell lymphoma and had an indolent clinical course, and 2 patients (one who transformed to large B-cell lymphoma, and the other who was initially diagnosed with a high-grade B-cell lymphoma) had an aggressive clinical course. Immunophenotypically, the neoplastic B cells expressed CD5, CDK6, and cytoplasmic retinoblastoma 1 protein in all cases, expressed phospho-RB, p27kip1, and cyclin D2 in most cases, and uniformly lacked expression of all other cyclins. In 4 cases, the CDK6 translocation partner was kappa immunoglobulin light-chain gene; and in the fifth case, the CDK6 translocation partner was unknown. These distinct clinicopathologic and cytogenetic features distinguish the CDK6 translocation-associated BLPDs (CDK6-BLPDs) from other mature B-cell lymphomas.
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PMID:Clinicopathologic features of CDK6 translocation-associated B-cell lymphoproliferative disorders. 1914 99

The BCL6 transcriptional repressor protein has been shown to promote B-cell lymphoma in transgenic mouse models. The mechanism by which BCL6 transforms primary B cells is unclear, although repression of the p53 tumor suppressor is thought to play a role. Here, we showed that BCL6 has critical oncogene functions that are independent of p53 repression. We found that BCL6 cooperates with constitutive CD40 signaling to rapidly transform p53-deficient primary mouse B cells in vitro. Constitutive CD40 signaling alone does not transform p53-deficient B cells, indicating that BCL6 acts specifically as an immortalizing oncogene in this system. The BCL6 transformed B cells are polyclonal and form polyclonal tumors. At the initiation of the cultures, BCL6 does not significantly alter cell cycle progression, but it does promote increased cell survival. Early cultures of BCL6-expressing B cells exhibited marked repression of ATR and p27kip1 but not other BCL6 target genes, suggesting that the ATR and p27kip1 genes have key early roles in mediating BCL6 transformation function. BCL6-transformed cell lines exhibited further decreases of ATR and p27kip1 expression plus strong decreases in Blimp1 and PDCD2 expression. Our study provides important clues about the critical target genes used by BCL6 to transform primary B cells and indicates that the CD40 signaling pathway can collaborate with BCL6 in the transformation of primary B cells. Thus, our study demonstrates a rapid in vitro system to analyze the transformation function of BCL6.
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PMID:BCL6 cooperates with CD40 stimulation and loss of p53 function to rapidly transform primary B cells. 1940 21

In diffuse large B-cell lymphoma (DLBCL), many oncogenic microRNAs (OncomiRs) are highly expressed to promote disease development and progression by inhibiting the expression and function of certain tumor suppressor genes, and these OncomiRs comprise a promising new class of molecular targets for the treatment of DLBCL. However, most current therapeutic studies have focused on a single miRNA, with limited treatment outcomes. In this study, we generated tandem sequences of 10 copies of the complementary binding sequences to 13 OncomiRs and synthesized an interfering long non-coding RNA (i-lncRNA). The highly-expressed i-lncRNA in DLBCL cells would compete with the corresponding mRNAs of OncomiR target genes for binding OncomiRs, thereby effectively consuming a large amount of OncomiRs and protecting many tumor suppressor genes. The in vitro experiments confirmed that the i-lncRNA expression significantly inhibited cell proliferation, induced cell cycle arrest and apoptosis in DLBCL cell lines, mainly through upregulating the expression of PTEN, p27kip1, TIMP3, RECK and downregulating the expression of p38/MAPK, survivin, CDK4, c-myc. In the established SUDHL-4 xenografts in nude mice, the treatment strategy involving adenovirus-mediated i-lncRNA expression significantly inhibited the growth of DLBCL xenografts. Therefore, this treatment would specifically target the carcinogenic effects of many OncomiRs that are usually expressed in DLBCL and not in normal cells, such a strategy could improve anti-tumor efficacy and safety and may be a good prospect for clinical applications.
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PMID:Therapeutic strategy with artificially-designed i-lncRNA targeting multiple oncogenic microRNAs exhibits effective antitumor activity in diffuse large B-cell lymphoma. 2717 95

DNA methylation is an epigenetic mechanism controlling gene expression without affecting DNA sequences, and aberrant DNA methylation patterns are features of a number of diseases. Notably, epigenetic errors in cancer cells have been intensively studied over the last two decades in humans; however, little is known concerning dogs and cats. To analyze DNA methylation and gene expression changes in feline lymphoma cells, we added the DNA methylation inhibitor 5-aza-2'-deoxycytidine (5-aza) to three cell lines (3281 and FT-1 cells derived from T-cell lymphoma and MS4 cells derived from B-cell lymphoma). Adding 5-aza significantly retarded cell growth in a dose-dependent manner in all cell lines, and there were aberrant gene expression patterns. Transcription factor Sox11 expression in 3281 cells was de-repressed by 5-aza treatment, and subsequent promoter DNA demethylation was analyzed by bisulfite sequencing. Cell cycle analysis suggested that inhibition of cell growth was due to DNA replication arrest, and this supported the result of increased expression of p27kip1 gene which disturbed cells of 3281 and FT-1 entering the S phase. In this study, 5-aza suppressed the growth of feline lymphoma cells, but further experiments with normal lymph cells are necessary to confirm specificity of this drug treatment and to expand it for clinical use.
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PMID:DNA methylation inhibitor causes cell growth retardation and gene expression changes in feline lymphoma cells. 2865 19