UMLS:C0019829 - FACTA Search

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Query: UMLS:C0019829 (Hodgkin's disease)
30,247 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Three cases of (3;13)(q27;q14) translocation observed in different histological types of non-Hodgkin lymphomas (NHLs) are reported here. This new recurring translocation in NHL was secondary in at least two of the patients because it was associated with another specific change [i.e., t(8;14) (q24;q32) in Burkitt lymphoma and t(14;18)(q32;q21) in typical follicular lymphoma]. In two of the cases for which molecular analysis was performed, a rearrangement of the LAZ-3/BCK-6 gene was found.
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PMID:Translocation (3;13)(q27;q14): a nonrandom and probably secondary structural change in non-Hodgkin lymphomas. 961 13

Primary mediastinal B-cell lymphoma (PMBL) shows chromosome 9p anomalies in 50% of cases. Based on reports that p16INK4A gene, located on this chromosomal arm, is frequently altered in aggressive lymphomas, we analysed for alterations of this gene in 27 cases of PMBL, which were part of a series of 32 PMBL cases that have been characterized for alterations in c-myc, p53, N-ras, bcl-1, bcl-2, bcl-6 and for Epstein-Barr virus (EBV) infection. Four cases showed p16INK4A gene anomalies, including three with promoter methylation and one homozygous deletion. Eight PMBLs showed c-myc rearrangements. Three additional cases showed sequence variations in the c-myc P2 promoter, two of which consisted of the same germline variation involving a novel polymorphic XhoI site. Four tumours contained p53 gene mutations and three had clonal EBV infection. One case had a bcl-6 rearrangement. In conclusion, our study shows that p16INK4, c-myc and p53 alterations occur in 15%, 25% and 13% of PMBLs, respectively. EBV monoclonality was found in 9% of cases, whereas no abnormality was detected in bcl-1, bcl-2 and N-ras. Thus, none of the common genetic aberrations seen in other types of non-Hodgkin's lymphomas appears to be stringently involved in the pathogenesis of this unique lymphoma type.
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PMID:Molecular features of primary mediastinal B-cell lymphoma: involvement of p16INK4A, p53 and c-myc. 1052 30

A new monoclonal antibody (MUM1p) was used to study the cell/tissue expression of human MUM1/IRF4 protein, the product of the homologous gene involved in the myeloma-associated t(6;14) (p25;q32). MUM1 was expressed in the nuclei and cytoplasm of plasma cells and a small percentage of germinal center (GC) B cells mainly located in the "light zone." Its morphologic spectrum ranged from that of centrocyte to that of a plasmablast/plasma cell, and it displayed a phenotype (MUM1(+)/Bcl-6(-)/Ki67(-)) different from that of most GC B cells (MUM1(-)/Bcl-6(+)/Ki67(+)) and mantle B cells (MUM1(-)/Bcl-6(-)/Ki67(-)). Polymerase chain reaction (PCR) analysis of single MUM1(+ )cells isolated from GCs showed that they contained rearranged Ig heavy chain genes with a varying number of V(H) somatic mutations. These findings suggest that these cells may represent surviving centrocytes and their progeny committed to exit GC and to differentiate into plasma cells. MUM1 was strongly expressed in lymphoplasmacytoid lymphoma, multiple myeloma, and approximately 75% of diffuse large B-cell lymphomas (DLCL-B). Unlike normal GC B cells, in which the expression of MUM1 and Bcl-6 were mutually exclusive, tumor cells in approximately 50% of MUM1(+) DLCL-B coexpressed MUM1 and Bcl-6, suggesting that expression of these proteins may be deregulated. In keeping with their proposed origin from GC B cells, Hodgkin and Reed-Sternberg cells of Hodgkin's disease consistently expressed MUM1. MUM1 was detected in normal and neoplastic activated T cells, and its expression usually paralleled that of CD30. These results suggest that MUM1 is involved in the late stages of B-cell differentiation and in T-cell activation and is deregulated in DLCL-B. (Blood. 2000;95:2084-2092)
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PMID:A monoclonal antibody (MUM1p) detects expression of the MUM1/IRF4 protein in a subset of germinal center B cells, plasma cells, and activated T cells. 1070 78

Fenretinide (4-HPR) is a synthetic retinoid with cancer chemopreventative potential and clinically manageable side effects, compared to the prototype retinoid, all-trans retinoic acid (RA). 4-HPR has been shown to modulate cell proliferation and induce apoptosis in a variety of human tumor cell types, but its effects on B-cell non-Hodgkin's lymphomas (NHL-B) have not been explored. Treatment of Burkitt's lymphoma Mutu I cells with 3 microM 4-HPR is accompanied by growth arrest, induction of apoptosis, and restricted progression of the cell cycle at the G(1)/S checkpoint. We also observed that 4-HPR elicited a reduced expression of bcl-6 in these cells, which supports the proposed role of bcl-6 as an anti-apoptotic gene. While 4-HPR treatment had no effect on total Rb gene expression, it significantly reduced the state of hyperphosphorylation of Rb, resulting in the predominant existence of Rb in the underphosphorylated state.
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PMID:Apoptosis and restriction of G(1)/S cell cycle by fenretinide in Burkitt's lymphoma mutu I cell line accessed with bcl-6 down-regulation. 1102 25

Splenic marginal zone lymphoma (SMZL) has been recognized as a distinctive type of small B cell lymphoma, and defined on the basis of its morphological, phenotypic, clinical and molecular characteristics. In spite of this, the borders of the entity, the homogeneity of the cases and the presumably cell origin of SMZL remain controversial issues. The frequency of mutation in the 5' non-coding region of the bcl-6 gene has been used as a marker of germinal center derivation, which may be used to establish the molecular heterogeneity of different non-Hodgkin lymphoma (NHL) types. This roughly parallels the characteristics and frequency of the somatic hypermutations found in the immunoglobulin heavy chain variable region (IgVH) genes. This study analyzed mutations of bcl-6 in the 5' non-coding region in 22 SMZL cases and, for the purpose of comparison with different B cell subsets, in microdissected germinal centers, mantle zones and marginal zone subpopulations from reactive splenic lymphoid follicles. A majority of the SMZL cases studied, 19/22 (87%), bear unmutated bcl-6 gene, while mutation was only observed in 3/22 (13%) cases. Analysis of normal B cell subpopulations showed bcl-6 hypermutation in 3/10 (30%) germinal center clones, 5/14 (35%) marginal zone clones; and unmutated sequences in all clones derived from mantle cells. The frequency of these mutations in normal spleen confirms previous findings on the hypermutation IgVH process in normal B cell populations. The data presented here support the existence of molecular heterogeneity in this entity, and give additional results in favor of the hypothesis that, in spite of initial morphological observations, a significant proportion of SMZL cases could derive from an unmutated naive precursor, different from the marginal zone, and possibly located in the mantle zone of splenic lymphoid follicles. Thus the marginal zone differentiation of these tumors could be related more with the splenic microenvironment than it is to the histogenetic characteristics of the tumor.
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PMID:Molecular heterogeneity of splenic marginal zone lymphomas: analysis of mutations in the 5' non-coding region of the bcl-6 gene. 1136 66

The BCL-6 proto-oncogene is expressed in germinal center B lymphocytes, in their neoplastic counterparts, and in a subpopulation of germinal center and perifollicular T lymphocytes. Rearrangements and/or mutations of the 5' noncoding region of the bcl-6 gene have been demonstrated in a large majority of diffuse large B cell lymphomas. Some, but not all, of these genetic alterations lead to dysregulation of the protein. Recently, anaplastic large cell lymphomas with T and null cell phenotypes, as well as T lymphoblastic lymphomas, have also been reported to exhibit immunoreactivity to the anti-BCL-6 antibody. We collected 33 T cell non-Hodgkin lymphomas (T-NHLs) and analyzed their expression of the BCL-6 protein by immunohistochemistry and investigated the organization of the bcl-6 gene by Southern blot and single strand conformation polymorphism (SSCP). The expression of BCL-6 was demonstrated in 37.5% of lymphoblastic (LBL), 40% of anaplastic large cell (ALCL), and 33% of peripheral T cell lymphomas (PTCL). BCL-6-positive malignant cells exhibited the CD4+ or CD4+/CD8+ phenotype. The bcl-6 gene was in a germline configuration in all T-NHLs examined, and a mutation at the first exon-intron boundary region structure of the wild-type bcl-6 gene was detected in 3 of 12 PTCL. One case of PTCL with mutations of the 5' noncoding region expressed BCL-6. In conclusion, expression of the BCL-6 protein is demonstrable independently of bcl-6 alterations in T-NHLs. This further suggests that molecular mechanisms other than rearrangements and/or mutations of the 5' noncoding region of the bcl-6 gene can result in expression of the protein. Whether these lymphomas arose from T cells expressing BCL-6 or expressed BCL-6 as part of the malignant transformation process needs to be determined. Finally, structural alterations of bcl-6 are rare in T-NHLs, but mutations do occur in the 5' noncoding region. We suggest that expression of BCL-6 in T cells may facilitate lymphomagenesis by repressing critical cytokines and cell cycle regulators.
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PMID:Alterations on the 5' noncoding region of the BCL-6 gene are not correlated with BCL-6 protein expression in T cell non-Hodgkin lymphomas. 1174 39

The HIV epidemic in the Asian subcontinent has a significant impact on India. Patients with AIDS have an increased risk of developing non-Hodgkin lymphoma (NHL). In this study, we have investigated the pattern of distribution of lymphoid neoplasms and also studied the Epstein-Barr virus (EBV)-association and p53 expression in 35 HIV-positive patients from India. The biopsy samples were studied for histology and for expression of CD20, CD3, CD15, CD30, light chains, CD138, bcl-6, epithelial membrane antigen, EBV-latent membrane protein-1, and p53 protein. In situ hybridization was performed with digoxigenin-labeled anti-sense EBV-encoded nuclear RNA-1 (EBER-1) probe. Polymerase chain reaction (PCR) was performed on DNA extracted from paraffin sections for EBV-subtype analysis. The 35 cases included 7 cases of Hodgkin disease (HD), 4 cases of plasmacytoma (PL), and 24 cases of NHL. Among the cases of NHL, 3 were Burkitt lymphoma (BL), 4 were diffuse large B-cell lymphoma (DLBL) of centroblastic type (CBL), 10 were DLBL of immunoblastic type (IBL), 4 were high-grade B-cell lymphoma (unspecified) and the rest were other subtypes. EBV-association was noted in all cases of HD, 2 of 3 BL, and 3 of 10 IBL. PCR analysis of the EBNA-3C gene revealed amplimers corresponding to type A. A p53 protein overexpression was noted in 6 of 10 IBLs, 1 of 3 BLs, 2 of 3 CBLs, and 5 of 7 cases of HD. This is the first reported study of lymphoid malignancies in HIV-positive individuals from India.
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PMID:Lymphoid neoplasms in HIV-positive individuals in India. 1183 89

The PLZF (promyelocytic leukemia zinc finger) transcriptional repressor, when fused to retinoic acid receptor alpha (RARalpha), causes a refractory form of acute promyelocytic leukemia. The highly conserved N-terminal BTB (bric a brac, tramtrack, broad complex)/POZ domain of PLZF plays a critical role in this disease, since it is required for transcriptional repression by the PLZF-RARalpha fusion protein. The crystal structure of the PLZF BTB domain revealed an obligate homodimer with a highly conserved charged pocket formed by apposition of the two monomers. An extensive structure-function analysis showed that the charged pocket motif plays a major role in transcriptional repression by PLZF. We found that mutations of the BTB domain that neutralize key charged pocket residues did not disrupt dimerization, yet abrogated the ability of PLZF to repress transcription and led to the loss of interaction with N-CoR, SMRT, and histone deacetylases (HDACs). We extended these studies to the Bcl-6 protein, which is linked to the pathogenesis of non-Hodgkin's lymphomas. In this case, neutralizing the charged pocket also resulted in loss of repression and corepressor binding. Experiments with purified protein showed that corepressor-BTB interactions were direct. A comparison of the PLZF, Bcl-6, and the FAZF (Fanconi anemia zinc finger)/ROG protein shows that variations in the BTB pocket result in differential affinity for corepressors, which predicts the potency of transcriptional repression. Thus, the BTB pocket represents a molecular structure involved in recruitment of transcriptional repression complexes to target promoters.
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PMID:Critical residues within the BTB domain of PLZF and Bcl-6 modulate interaction with corepressors. 1186 59

The incidence of B-cell non-Hodgkin lymphomas (B-NHL) at nodal and extranodal sites is fairly different. Follicular lymphomas (FL) occur predominantly at nodal sites and rarely in the gastrointestinal tract, while marginal zone lymphomas (MZL) of the mucosa-associated lymphatic tissue (MALT) type predominate in the digestive organs and especially in the stomach. We report a 72-year-old female patient admitted for gastroscopy because of epigastric pain. The antral biopsies showed dense lymphocytic infiltrates, partially forming follicles with widened marginal zones and monocytoid cells. Multiple lymphoepithelial lesions (LEL) were also observed. A MZL of the MALT type was suspected morphologically. Immunohistochemical analysis revealed the lymphatic infiltrates to be CD20, bcl-2, bcl-6 and CD10 positive, and negative for CD43, CD5 and cyclin D1. PCR-based analysis showed a JH/bcl-2 rearrangement, corresponding to the translocation t(14;18). An extranodal FL mimicking MZL was diagnosed. The present case is remarkable, as it demonstrates that the detection of LEL and monocytoid B-cells, although suggestive for MZL, is not entirely specific and can also be observed in FL. Pathologists should be aware of this diagnostic pitfall in classifying gastric B-NHL. In equivocal cases, a careful morphological examination, supported by specific immunohistochemical and molecular findings, should lead to the correct diagnosis.
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PMID:Primary gastric follicular lymphoma with parafollicular monocytoid B-cells and lymphoepithelial lesions, mimicking extranodal marginal zone lymphoma of MALT. 1246 20

Chromosomal translocations involving t(14;18)(q32;q21) and the chromosome 3q27 region are common in B-cell non-Hodgkin lymphoma of germinal center cell origin. Grade 3B follicular lymphoma (FL), consisting almost exclusively of centroblasts, is a distinct subgroup of follicular lymphomas that has more in common clinically with the aggressive diffuse large B-cell lymphomas than with their indolent FL grade 1 and 2 counterparts. We studied the cytogenetic and molecular genetic aberrations by classic cytogenetics, polymerase chain reaction, Southern blot hybridization, and fluorescence in situ hybridization, with special emphasis on t(14;18), affecting bcl-2, and 3q27 rearrangement, affecting bcl-6, in 32 cases of FL grade 3B. Three distinctive subgroups were identified based upon the existence of breakpoint 3q27, a translocation t(14;18), or the absence of both. Group I involved a t(14;18) and no 3q27 aberrations (n = 13); group II was without a t(14;18) and without 3q27 aberrations (n = 9), but had other cytogenetic aberrations; and group III was without a t(14;18) but with aberrations involving 3q27 (n = 10). None of the FL grade 3B cases harbored both a t(14;18) and 3q27 aberration. These results, in particular the finding of a mutual exclusiveness of bcl-2 and bcl-6 rearrangement, indicate at least 3 different pathways of oncogenesis in FL grade 3B. FL grade 3B with bcl-2 rearrangement probably is part of the same entity as the other follicular lymphomas (1, 2, 3A), whereas the cases with 3q27 abnormalities or other unrelated translocations are more closely related to the majority of diffuse large-cell lymphomas of germinal center cell origin.
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PMID:Follicular lymphoma grade 3B includes 3 cytogenetically defined subgroups with primary t(14;18), 3q27, or other translocations: t(14;18) and 3q27 are mutually exclusive. 1252 93

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