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)

Post-transplant lymphoproliferative disorders (PTLD) represent a serious complication of solid organ and allogeneic bone marrow transplantation. PTLD generally display B-cell lineage derivation, involvement of extranodal sites, aggressive histology and clinical behaviour, and frequent association with EBV infection. The occurrence of IgV mutations in the overwhelming majority of PTLD documents that malignant transformation targets germinal centre (GC) B-cells and their descendants both in EBV-positive and EBV-negative cases. Analysis of phenotypic markers of B-cell histogenesis, namely BCL6, MUM-1 and CD138, allows further distinction of PTLD histogenetic categories. PTLD expressing the BCL6(+)/MUM1(+/-)/CD138(-) profile reflect B-cells actively experiencing the GC reaction and comprise diffuse large B-cell lymphoma (DLBCL) centroblastic and Burkitt lymphoma. PTLD expressing the BCL6(-)/MUM1(+)/CD138(-) phenotype putatively derive from B-cells that have concluded the GC reaction and comprise the majority of polymorphic PTLD and a fraction of DLBCL. A third group of PTLD is reminiscent of post-GC and pre- terminally differentiated B-cells that show the BCL6(-)/MUM1(+)/CD138(+) phenotype and are morphologically represented by either polymorphic PTLD or DLBCL immunoblastic. The molecular pathogenesis of PTLD involves infection by oncogenic viruses, namely Epstein-Barr virus, as well as genetic or epigenetic alterations of several cellular genes. At variance with lymphoma arising in immunocompetent hosts, whose genome is relatively stable, a fraction of PTLD are characterized by microsatellite instability as a consequence of defects in the DNA mismatch repair mechanism. Apart from microsatellite instability, molecular alterations of cellular genes recognized in PTLD include alterations of c-MYC, BCL-6, p53, DNA hypermethylation, and aberrant somatic hypermutation of proto-oncogenes.
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PMID:Post-transplant lymphoproliferative disorders: molecular basis of disease histogenesis and pathogenesis. 1621 37

Interferon (IFN) consensus sequence-binding protein/IFN regulatory factor 8 (IRF8) is a transcription factor that regulates the differentiation and function of macrophages, granulocytes, and dendritic cells through activation or repression of target genes. Although IRF8 is also expressed in lymphocytes, its roles in B cell and T cell maturation or function are ill defined, and few transcriptional targets are known. Gene expression profiling of human tonsillar B cells and mouse B cell lymphomas showed that IRF8 transcripts were expressed at highest levels in centroblasts, either from secondary lymphoid tissue or transformed cells. In addition, staining for IRF8 was most intense in tonsillar germinal center (GC) dark-zone centroblasts. To discover B cell genes regulated by IRF8, we transfected purified primary tonsillar B cells with enhanced green fluorescent protein-tagged IRF8, generated small interfering RNA knockdowns of IRF8 expression in a mouse B cell lymphoma cell line, and examined the effects of a null mutation of IRF8 on B cells. Each approach identified activation-induced cytidine deaminase (AICDA) and BCL6 as targets of transcriptional activation. Chromatin immunoprecipitation studies demonstrated in vivo occupancy of 5' sequences of both genes by IRF8 protein. These results suggest previously unappreciated roles for IRF8 in the transcriptional regulation of B cell GC reactions that include direct regulation of AICDA and BCL6.
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PMID:Regulation of the germinal center gene program by interferon (IFN) regulatory factor 8/IFN consensus sequence-binding protein. 1638 May 10

We assessed primary cutaneous large B-cell lymphoma, leg type (PCLBCL, leg type; n = 13), and primary cutaneous follicle center lymphoma (PCFCL; n = 19) for somatic hypermutation (SHM) of BCL6, and aberrant SHM of MYC, RhoH/TTF, and PAX5. We demonstrate SHM of BCL6 in 8 PCLBCLs (62%), leg type, and 7 PCFCL patients (37%), and aberrant SHM in PAX5, RhoH/TTF, and/or MYC in 7 PCLBCLs (54%), leg type, and 10 PCFCL patients (53%). The majority of mutations consisted of single base-pair substitutions (n = 54) with rare deletions/insertions (n = 4), and displayed molecular features typical of the SHM process. Quantitative real-time PCR and immunohistochemical stainings for activation-induced cytidine deaminase, which is indispensable for SHM, demonstrated significantly higher expression in PCLBCL, leg type. Our results suggest that (aberrant) SHM may contribute to the pathogenesis of PCLBCL, leg type, and PCFCL and is not restricted to diffuse large B-cell lymphomas with an aggressive clinical behavior.
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PMID:Primary cutaneous follicle center lymphoma and primary cutaneous large B-cell lymphoma, leg type, are both targeted by aberrant somatic hypermutation but demonstrate differential expression of AID. 1650 80

The t(3;14)(q27;q32) is the most common translocation involving BCL6 in B-cell lymphoma. Although this translocation was predominantly associated with diffuse large B-cell lymphoma (DLBCL), recent studies have shown that it can also be found in follicular lymphomas (FL), often associated with a large cell component. To further investigate the relationship that might exist between this translocation and the phenotype of the tumors, we studied 34 lymphomas with a t(3;14)(q27;q32). Twenty cases were DLBCL, 14 FL and most cases, regardless of histology, were negative for the expression of CD10 (26/32, 81%). We identified the IGH switch region involved in the translocation for 32 cases. Our data indicate that in DLBCL most breakpoints involve the switch mu (17/19; 89%), whereas in FL most involve a switch gamma (9/13; 70%) (P=0.0016, Fisher's exact test). This correlation between the histology and the structure of the translocated allele suggests that the lymphomas with Smu and Sgamma translocations may originate from different cells, or that the substituted regulatory regions that come to deregulate BCL6 may affect the presentation of the disease.
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PMID:Two patterns of chromosomal breakpoint locations on the immunoglobulin heavy-chain locus in B-cell lymphomas with t(3;14)(q27;q32): relevance to histology. 1661 46

Cytogenetic data for T-cell/histiocyte-rich large B-cell lymphoma (THRLBCL) are scarcely available. We report here a case of THRLBCL with a near-tetraploid karyotype and complex chromosomal aberrations, without rearrangement of BCL2 or BCL6, and characterized pathologically by a variegated morphologic appearance with areas resembling nodular lymphocyte-predominant Hodgkin's lymphoma (NLPHL).
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PMID:T-cell/histiocyte-rich large B-cell lymphoma associated with a near-tetraploid karyotype and complex genetic abnormalities. 1685 72

We previously developed a multivariate model based on the RNA expression of 6 genes (LMO2, BCL6, FN1, CCND2, SCYA3, and BCL2) that predicts survival in diffuse large B-cell lymphoma (DLBCL) patients. Since LMO2 emerged as the strongest predictor of superior outcome, we generated a monoclonal anti-LMO2 antibody in order to study its tissue expression pattern. Immunohistologic analysis of over 1200 normal and neoplastic tissue and cell lines showed that LMO2 protein is expressed as a nuclear marker in normal germinal-center (GC) B cells and GC-derived B-cell lines and in a subset of GC-derived B-cell lymphomas. LMO2 was also expressed in erythroid and myeloid precursors and in megakaryocytes and also in lymphoblastic and acute myeloid leukemias. It was rarely expressed in mature T, natural killer (NK), and plasma cell neoplasms and was absent from nonhematolymphoid tissues except for endothelial cells. Hierarchical cluster analysis of immunohistologic data in DLBCL demonstrated that the expression profile of the LMO2 protein was similar to that of other GC-associated proteins (HGAL, BCL6, and CD10) but different from that of non-GC proteins (MUM1/IRF4 and BCL2). Our results warrant inclusion of LMO2 in multivariate analyses to construct a clinically applicable immunohistologic algorithm for predicting survival in patients with DLBCL.
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PMID:The oncoprotein LMO2 is expressed in normal germinal-center B cells and in human B-cell lymphomas. 1703 24

The transit of T cell-activated B cells through the germinal center (GC) is controlled by sequential activation and repression of key transcription factors, executing the pre- and post-GC B cell program. B cell lymphoma (BCL) 6 and IFN regulatory factor (IRF) 8 are necessary for GC formation and for its molecular activity in Pax5+PU.1+ B cells. IRF4, which is highly expressed in BCL6- GC B cells, is necessary for class switch recombination and the plasma cell differentiation at exit from the GC. In this study, we show at the single-cell level broad coexpression of IRF4 with BCL6, Pax5, IRF8, and PU.1 in pre- and post-GC B cells in human and mouse. IRF4 is down-regulated in BCL6+ human GC founder cells (IgD+CD38+), is absent in GC centroblasts, and is re-expressed in positive regulatory domain 1-positive centrocytes, which are negative for all the B cell transcription factors. Activated (CD30+) and activation-induced cytidine deaminase-positive extrafollicular blasts coexpress Pax5 and IRF4. PU.1-negative plasma cells and CD30+ blasts uniquely display the conformational epitope of IRF4 recognized by the MUM1 Ab, an epitope that is absent from any other IRF4+PU.1+ lymphoid and hemopoietic subsets. Low grade B cell lymphomas, representing the malignant counterpart of pre- and post-GC B cells, accordingly express IRF4. However, a fraction of BCL6+ diffuse large B cell lymphomas express IRF4 bearing the MUM1 epitope, indicative of a posttranscriptional modification of IRF4 not seen in the normal counterpart.
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PMID:Stages of germinal center transit are defined by B cell transcription factor coexpression and relative abundance. 1708 8

Resveratrol is a polyphenolic compound that exhibits anti-proliferative and anti-inflammatory activities. BCL6, a transcriptional repressor frequently translocated in lymphomas, including diffuse large B-cell lymphoma (DLBCL) and transformed follicular lymphoma (FL), regulates germinal center B-cell differentiation. We report herein that resveratrol treatment of human LY8 follicular lymphoma cells leads to an accumulation of LY8 cell in G0/G1 phase and apoptosis. Resveratrol decreased the expression of BCL6 protein, concomitant with the increased expression of several BCL6 regulated gene products, including p27, p53 and CD69. In addition, resveratrol reduces Myc expression in LY8 cells. These results demonstrate for the first time that resveratrol inhibits a BCL6-linked pathway and suggest that loss of BCL6 expression may represent a key event underlying the anti-proliferative activities of resveratrol on LY8 cells. The use of resveratrol to treat aggressive lymphomas with BCL6 and/or MYC translocations may prove useful as an effective therapy.
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PMID:Resveratrol induces apoptosis in transformed follicular lymphoma OCI-LY8 cells: evidence for a novel mechanism involving inhibition of BCL6 signaling. 1708 97

Chromosome analysis of a patient with intravascular large B-cell lymphoma (IVL) revealed a complex, near-tetraploid karyotype with 83 chromosomes. Abnormalities included a t(11;14)(q13;q32), which was confirmed with both interphase fluorescence in situ hybridization (FISH) using an IGH/cyclin D1 dual-color, dual-fusion probe set and cyclin D1 immunohistochemical analysis. Abnormality of 3q was also evident. Interphase FISH analysis with a dual-color, break-apart probe set confirmed rearrangement of BCL6. To our knowledge, this is the first report of these abnormalities in IVL.
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PMID:Intravascular large B-cell lymphoma associated with a near-tetraploid karyotype, rearrangement of BCL6, and a t(11;14)(q13;q32). 1711 87

CD56 (NCAM), a neural adhesion molecule, is normally expressed on natural killer cells and subsets of T cells and is commonly seen on hematolymphoid neoplasms such as plasma cell myeloma and acute myelogenous leukemia. It is uncommon in B-cell lymphoma. From 2001 to 2003 a cohort of 20 cases of CD56 B-cell lymphomas was identified by flow cytometry (<0.5% of all B-cell lymphomas studied) during a 2-year period. Most (90%) expressed CD10 and 5/5 tested cases were BCL6, suggesting a follicular origin. An extranodal disease presentation was seen in 45% and may be related to CD56 expression. These CD56 B-cell lymphomas may represent a new subset of large B-cell lymphoma. The relationship of cells with this antigenic profile to normal B-cell differentiation is explored.
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PMID:CD56-positive large B-cell lymphoma. 1712 31


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