Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0019829 (Hodgkin's disease)
 30,247 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Using three separate bcl-2 probes, we examined involvement of the bcl-2 gene in Japanese patients with non-Hodgkin's B-cell lymphomas. Of 52 patients with follicular lymphoma (FL), 24 had rearrangements. In a group of 50 patients with diffuse lymphoma, three of 32 patients with diffuse large cell lymphoma had rearrangements. The frequency of rearrangements in each of these groups, as detected by both major and minor breakpoint cluster region probes, was compatible with that found in other Far Eastern studies. However, the difference in frequency between the groups studied in the Far East and the West was significant, and these two geographically distinct populations also displayed a difference in the breakpoint distribution. In the immunophenotype study of 33 patients with FL, the expression of CD10 antigen correlated with bcl-2 involvement, whereas none of the other B markers emerged as parameters to distinguish between the two lymphoma groups; those with, and without, the rearrangements.
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PMID:Geographical aspects of bcl-2 gene involvement in Japanese patients with non-Hodgkin's B-cell lymphomas. 158 86

B-cell associated antigens are frequently expressed by the Reed-Sternberg (RS) cells of lymphocyte predominance (LP) Hodgkin's disease (HD) and are sometimes expressed by those of nodular sclerosis (NS) and mixed cellularity (MC) HD. Clonal immunoglobulin gene rearrangements have been detected in some HD cases as well. These findings suggest that at least some cases of HD may be of B-cell derivation. Rearrangements of the bcl-2 gene, associated with the t(14;18)(q32;q21) are present in more than 75% of follicular and 30% of diffuse lymphomas of B-cell origin, suggesting that this translocation plays an important role in B-cell lymphomagenesis. In this study, we investigated 34 cases of HD (10 LP, 14 NS, and 10 MC) for bcl-2 gene rearrangements to determine if this B-cell lymphoma-associated translocation also plays a role in the pathogenesis of HD. The cases of HD were analyzed by Southern blot hybridization, using DNA probes that detect the major and minor breakpoint cluster regions and a 5'bcl-2 breakpoint region recently cloned and found to be involved in B-cell chronic lymphocytic leukemia, and by the polymerase chain reaction (PCR), using oligonucleotides capable of amplifying and detecting the major breakpoint region (mbr) and minor cluster region (mcr) breakpoint regions in t(14;18). bcl-2 translocations were not detected in any of the 34 cases of HD by Southern blot hybridization or by PCR. This is in spite of the fact that RS cells expressing B-cell-associated antigen CD20 were detectable in 7/8 cases of LP HD and 6/24 cases of NS and MC HD with monoclonal antibody L26. Therefore, these results indicate that the bcl-2 gene translocation does not play an important role in the pathogenesis of HD and did not provide evidence for the B-cell origin of HD.
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PMID:The bcl-2 gene translocation is undetectable in Hodgkin's disease by Southern blot hybridization and polymerase chain reaction. 163 63

The bcl-2 proto-oncogene, rearranged and deregulated in B-cell lymphomas bearing the t(14;18) translocation, encodes an inner mitochondrial membrane protein that blocks apoptotic cell death. We have developed a sensitive immunofluorescence assay for the single- and multicolor flow cytometric analysis of bcl-2 protein in relation to other markers and cell cycle, based on a fixation-permeation step of cells with paraformaldehyde and Triton X100 and the use of a bcl-2 specific monoclonal antibody (MoAb). As an application of this method, we have examined the expression of bcl-2 in normal and neoplastic lymphoid cells. We have found that greater than 80% of normal T-and B-cells are bcl-2 positive; following in vitro mitogen activation, the bcl-2 reactivity decreased slightly in the former but markedly in latter cells. In both cases the bcl-2 expression was not restricted to a specific phase of the cell cycle, as evidenced by two-color analysis. On lymphoblastoid cell lines, the bcl-2 staining intensity was variable and not necessarily correlated to molecular rearrangements of the bcl-2 gene. Among fresh B-cell non-Hodgkin's lymphomas (B-NHL), most sporadic Burkitt's cases were bcl-2 negative. Of four centroblastic-centrocytic cases with rearrangements of the bcl-2 gene, only two presented elevated amounts of bcl-2 protein, indicating that the levels of bcl-2 are not diagnostic of the translocation.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Flow cytometric detection of the mitochondrial BCL-2 protein in normal and neoplastic human lymphoid cells. 163 29

Twenty frozen and 55 paraffin sections of lymphnode specimens from 55 patients with pretreatment Hodgkin's disease (nodular sclerosis Hodgkin's disease, n = 45; mixed cellularity Hodgkin's disease, n = 10) were studied by immunohistochemistry and molecular analysis to determine the phenotype of Hodgkin's and Reed-Sternberg cells (HRS). In all cases the HRS cells were CD45-, and CD30+, and in 43/55 (78%) cases they were CD15+. In 48/55 cases (87%) HRS cells were reactive with at least one B-cell marker (CD19, CD20, CD22, CDw75, MB2), 8/55 cases (14.5%) showed reactivity (mainly cytoplasmic) of a subpopulation of HRS cells with the T-cell markers CD3 and beta F1. All cases that expressed T-cell antigens were also reactive with at least one B-cell marker. In frozen sections, a minority of HRS cells in each case studied showed cytoplasmic positivity for bcl-2 protein. Rearrangement of immunoglobulin heavy chain genes was detected in one case and of T-cell receptor beta chain genes in none. The authors were unable to confirm previous reports of bcl-2 gene rearrangement in Hodgkin's disease. The results strongly support a B lymphocytic origin of HRS cells.
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PMID:Expression of B-cell antigens by Hodgkin's and Reed-Sternberg cells. 165 57

Polymerase chain reaction (PCR) of bcl-2 provides an extremely sensitive method to detect minimal disease in approximately 50% of patients with non-Hodgkin's lymphomas (NHL). In an attempt to determine the clinical usefulness of this technique, we examined the bone marrow (BM) of 152 patients with advanced-stage NHL at the time of evaluation and after induction or salvage chemotherapy before autologous BM transplantation. The BM proved to be an accessible and reproducible tissue source to determine PCR positivity because all of the 102 patients examined had the same PCR-amplifiable breakpoint in their BM and lymph node. At the time of evaluation, PCR analysis in advanced-stage NHL patients added little additional information to morphologic analysis because each technique identified BM infiltration in approximately 70% of patients. PCR was significantly more useful in determining BM infiltration after induction or salvage therapy. At that time, approximately 50% of patients had morphologically normal BM, whereas PCR analysis remained positive in 100% of those with an amplifiable breakpoint. These observations were confirmed in a clinical trial attempting to induce remission in previously untreated low-grade advanced-stage NHL patients. In this series, PCR was positive in all patients after treatment although the BM was histologically uninvolved in 50% of cases, showing that conventional therapy did not eradicate bcl-2-positive cells.
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PMID:All advanced stage non-Hodgkin's lymphomas with a polymerase chain reaction amplifiable breakpoint of bcl-2 have residual cells containing the bcl-2 rearrangement at evaluation and after treatment. 174 87

Programmed cell death is a physiological, energy-consuming mechanism leading to suicide of the cell. Cell death is accomplished by the activation of endonucleases that fragment the cell's nuclear DNA. Some tumour cells remain susceptible to programmed death. These are hormone- and growth factor-dependent tumour cells. Hormone or growth factor deprivation induces signals leading to apoptosis. Other tumours gain strong resistance to apoptosis. One of the normal functions of the bcl-2 gene is to provide longevity to memory B cells. When this gene becomes translocated in follicular B cell lymphomas, it renders lymphoma cells resistant to apoptosis. Latent membrane protein encoded by an EBV gene, either by itself or by amplifying bcl-2, enables tumour cells (nasopharyngeal carcinoma; Reed-Sternberg cell of Hodgkin's disease) to resist apoptotic death. Loss of antioncogene p53 provides for resistance against programmed cell death. Breakdown of resistance to apoptosis in tumour cells can be achieved by oncolytic viruses; generation of lymphotoxin and tumour necrosis factor; monoclonal antibodies; transfection with plasmid vectors carrying p53; gamma irradiation; and certain chemotherapeutic agents.
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PMID:Programmed cell death (apoptosis): its virological and immunological connections (a review). 181 29

Recent evidence suggests that nodular lymphocyte predominance Hodgkin's disease (NLPHD) is a distinct entity that may be related to progressively transformed germinal centers, abnormal B-lymphoid hyperplasia, and low-grade B-cell lymphoma. bcl-2 is a marker for the translocation t(14;18)(q32;q21), which occurs in most follicular-derived B-cell lymphomas. Eleven cases of NLPHD and 19 cases of Hodgkin's disease of nodular sclerosis (NSHD) and mixed cellularity (MCHD) type were analyzed for immunoglobulin JH gene rearrangement. bcl-2 translocation was determined with Southern blot analysis and the polymerase chain reaction using biotin labeled probes to the major breakpoint region and the alkaline phosphatase reaction. All cases of NLPHD were negative for JH gene rearrangement and bcl-2 translocation. Cases of NSHD and MCHD were similarly negative for bcl-2, although three cases exhibited clonal JH gene rearrangements. These results confirm that a clonal B-cell population is not detected in NLPHD. Cases of NLPHD differ from most low-grade follicular B-cell lymphomas in that they lack bcl-2 gene rearrangement and t(14;18) translocation at the major breakpoint region.
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PMID:Absence of bcl-2 major breakpoint region and JH gene rearrangement in lymphocyte predominance Hodgkin's disease. Results of Southern blot analysis and polymerase chain reaction. 189 39

The 14;18 chromosomal translocation, characteristic of a significant fraction of non-Hodgkin's lymphomas, results from an apparent error in immunoglobulin gene rearrangement. Breakpoints for the 14;18 translocation cluster at defined sites on chromosomes 14 and 18 and this clustering has important implications for molecular diagnostic studies of lymphomas. The major effect of the 14;18 translocation is a transcriptional deregulation of the bcl-2 gene resulting in levels of the protein and mRNA that appear to be inappropriate for B cells at a comparable stage of differentiation. Gene transfer studies have demonstrated that inappropriate bcl-2 expression has subtle effects on cellular growth and survival without overt tumorigenic conversion. Biochemical studies have shown that bcl-2 is an integral membrane protein localized to the cytoplasmic side of cellular membranes, suggestive of a role in signal transduction, but no demonstrable biochemical activity has been reproducibly associated with the protein.
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PMID:The bcl-2 gene and protein in malignant lymphomas. 190 62

Hodgkin's disease, lymphocyte predominance type (nodular paragranuloma), is of germinal centre origin and the tumour cells have a B-cell phenotype. As the T(14;18) translocation, and the subsequent expression of bcl-2 protein by germinal centre cells, is the most characteristic finding of centroblastic-centrocytic lymphoma, we have tested a series of 11 cases of lymphocyte predominance Hodgkin's disease, using Southern blot analysis for the major breakpoint region and the minor breakpoint cluster region, polymerase chain reaction with primers for the major and minor breakpoint cluster region, and immunohistological studies with a monoclonal antibody specific for the bcl-2 protein. All three techniques gave negative results in the cases of Hodgkin's disease, establishing a clear differentiation from centroblastic-centrocytic lymphoma. These findings are useful in the differential diagnosis between the two entities and raise the question of the non-clonal nature of lymphocyte predominance Hodgkin's disease.
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PMID:Lymphocyte predominance Hodgkin's disease (nodular paragranuloma)--a bcl-2 negative germinal centre lymphoma. 191 88

We have examined 165 unselected cases of non-Hodgkin's lymphomas for rearrangements involving the t(14;18) major breakpoint region using a polymerase chain reaction (PCR) and direct sequencing of amplified major breakpoint region bcl-2/JH junctional regions. The lymphomas, diagnosed according to the updated Kiel classification, consisted of 33 centroblastic-centrocytic, 37 centroblastic, 27 immunocytic, 10 immunoblastic, 10 centrocytic, 2 lymphoblastic, 2 Ki-1-positive anaplastic large cell, 14 peripheral T-cell, and 4 unclassified lymphomas. In addition 18 chronic lymphocytic leukemias, 2 hairy cell leukemias, and 6 plasmacytomas were studied. In 17 cases a bcl-2/JH gene fusion sequence was amplified by PCR. A bcl-2/JH gene fusion was detected only in three lymphoma subgroups: 13 of 33 centroblastic-centrocytic (39%), 2 of 37 centroblastic (6%), and 2 of 27 immunocytic (8%) were positive. In two cases, major breakpoint region bcl-2 rearrangements verified by genomic Southern analysis were not detected by PCR. Direct sequencing of all 17 PCR-amplified, previously uncharacterized t(14;18) junctional regions provided corroborating evidence for the specificity of the assay. The procedure gave sequencing results even from limited amounts of lymphoma cells as obtained by fine needle aspiration of lymph nodes or from clinically uninvolved sites. Clone-specific sequences were identified due to the involvement of different JH segments, the variations among the exact JH and bcl-2 breakpoint positions, and the extensive incorporation of junctional region (D-) N-nucleotides. These clone-specific sequences allow accurate identification of clinically occult lymphoma cells and reduce the threat of false positive results. The finding of exceptionally long intervening sequences in some of the junctions and the partial homology with published DH segments in three cases support the view that some of the putative N-regions harbor DH regions.
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PMID:Frequency and structure of t(14;18) major breakpoint regions in non-Hodgkin's lymphomas typed according to the Kiel classification: analysis by direct DNA sequencing. 203 99


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