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

We have investigated seven cases of large cell lymphomas (LCL) developing simultaneously or metachronously to nodular lymphocyte-predominant Hodgkin's disease (nodular paragranuloma, NP) for the presence of EBV and the chromosomal translocation t(14;18) by use of the polymerase chain reaction (PCR). The expression of the bcl-2 oncogene product in these cases and in five cases of progressive transformation of germinal centres as a potential precursor of NP was detected immunohistochemically with the monoclonal antibodies bcl-2-100 and bcl-2-124. All cases investigated were negative for EBV genomic material. The chromosomal translocation t(14;18) was also absent. Expression of the bcl-2 oncogene could be detected only in one case of nodular paragranuloma and in an unrelated case of LCL. Hence, LCL developing out of NP differ from other germinal center derived high-grade lymphomas.
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PMID:[Bcl-2 in potentials precursors of nodular paragranuloma and its dedifferentiated variant (large cell B-lymphoma)]. 128 52

A series of 33 cases of Hodgkin's disease was investigated for the presence of the EBV encoded latent gene product LMP-1 and of CD23 using immunohistochemical techniques. The expression of bcl-2 was examined in a subset of cases. LMP-1 was detected in the Reed-Sternberg cells in 15 cases. Although LMP-1 is known to upregulate CD23 and bcl-2, there was no correlation between the expression of LMP-1 and the detection of CD23 and bcl-2 in Reed-Sternberg cells.
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PMID:The expression of the EBV latent membrane protein (LMP-1) is independent of CD23 and bcl-2 in Reed-Sternberg cells in Hodgkin's disease. 132 89

The following manuscript reviews data presented at the Cologne meeting relating to oncogene expression in Hodgkin's disease. Presented data ranged from investigations of oncogene expression in cell lines, where transcripts of unique size were identified and lineage related expressions of transcription factors described to detailed cytogenetic investigations of fresh Hodgkin's biopsy tissue. Particular attention was centred on discrepancies in the described expression of t(14; 18) and the molecular demonstration of translocated bcl-2 breakpoints in Hodgkin's disease. A large volume of data was presented relating to the relative expression of bcl-2 breakpoints by either genomic hybridization or hybridization following DNA amplification, the expression of the bcl-2 protein or the defined cytogenetic presence of the translocation. Certain other cytogenetic abnormalities of interest in Hodgkin's disease were discussed.
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PMID:Oncogenes in Hodgkin's disease. 133 73

The most recent sophisticated investigations have provided new and revealing, but also contradictory and controversial information on the biological nature and the cellular origin of Hodgkin and Reed-Sternberg cells (H-RS). Immunophenotypic analyses have shown variable phenotypic antigen expression; but, on balance the data suggest a lymphoid cell expressing T- and/or B-cell-associated markers and certain activation antigens while lacking immunological features of monocytes-macrophages or other lineages. Molecular genetic studies have demonstrated heterogenous findings with respect to rearrangements of T-cell receptor and immunoglobulin genes. Only a small percentage of the cases has rearrangements; this might be due to the threshold of sensitivity of the method combined with the scarcity of the malignant cells. Epstein-Barr virus (EBV) genomes are clonally integrated in the H-RS cells of about half the cases. The significance of these findings--whether EBV is a causative agent or an epiphenomenon--remains to be elucidated. H-RS cells express mRNA and proteins of various cytokines and cytokine receptors implying a predominant role for cytokines in the pathophysiology of HD. The mononuclear and polynuclear H-RS cells are capable of DNA synthesis and nuclear division; the lack of cellular division leads to multinuclearity through the process of endomitosis. Mutations and expression of only a limited number of oncogenes have been tested thus far. Whether the bcl-2 oncogene is involved in HD remains a matter of debate. Aneuploidy and non-random chromosomal abnormalities are the results of cytogenetic analyses of H-RS cells. However, no chromosomal marker specific for HD has yet been found. Thus, while studies of EBV involvement, growth factor production, oncogene expression and chromosomal abnormalities contributed a fair amount of new data on the nature of H-RS cells, only immunophenotyping and genotyping provided some indication of the cellular derivation: an activated lymphoid cell that possibly expresses oncogenes, that probably is infected with EBV, that most likely produces cytokines, that certainly has multiple karyotypic abnormalities.
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PMID:Recent results on the biology of Hodgkin and Reed-Sternberg cells. I. Biopsy material. 133 48

T-cell-rich B-cell lymphomas (TCRBCLs) are recently described, unusual non-Hodgkin's lymphomas that have a diffuse morphology, a predominance of reactive T-cells, and a minority of neoplastic B-cells. The clinical and pathological features of 19 TCRBCLs, all of which demonstrated B-cell clonality, are presented. These lymphomas generally affected older patients by widespread disease and usually were nodal in origin. Treatment varied, but continuous complete remissions (eight patients) were achieved only in those receiving chemotherapy directed at intermediate-grade lymphomas. Although morphologically heterogeneous, all cases resembled peripheral T-cell lymphomas (PTCLs); several TCRBCLs also contained Reed-Sternberg-like cells. Flow cytometry or frozen-section immunoperoxidase failed to detect monotypic immunoglobulin (Ig) in eight of eight cases tested. In contrast, paraffin immunoperoxidase was very useful diagnostically, showing large L26 (CD20-associated) positive cells scattered singly or in small clusters among numerous small T-cells (UCHL1[CD45RO] positive) in all cases. Monotypic cytoplasmic Ig was present in 16 of 19 cases, one of which exhibited plasmacytic differentiation. Southern blot analysis demonstrated relatively faint Ig JH and/or JK bands, indicating a small monoclonal B-cell population in nine of 11 cases, one of which also showed a bcl-2 rearrangement. No T-cell receptor gene rearrangements were observed. These results showed that TCRBCLs may be easily confused with PTCLs or occasionally confused with Hodgkin's disease. TCRBCLs are probably heterogeneous biologically; some cases are of follicular center cell origin. These lymphomas respond to chemotherapy directed at intermediate-grade lymphomas, apparently have a better prognosis than PTCLs, and seem to represent morphological variants of different types of large B-cell lymphomas.
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PMID:T-cell-rich B-cell lymphomas. A clinicopathologic study of 19 cases. 816 40

bcl-2 protein has been detected in surgical specimens and cultured permanent cell lines of non-Hodgkin's lymphomas and leukemias using enzyme immunohistochemistry and immunofluorescence with anti-bcl-2 monoclonal antibodies. Of 40 surgical specimens, bcl-2 protein was expressed in 50% of B-cell and 41% of T-cell lymphomas, both with and without the bcl-2 gene rearrangement. In investigations of 38 hematopoietic cell lines, bcl-2 protein was detected not only in lymphoid cell lines but also in myeloid cell lines. In situ hybridization and immunohistochemical analysis of reactive lymph nodes showed that lymphocytes in mantle zones and paracortical areas expressed bcl-2 protein consistent with the messenger RNA distribution and that germinal center cells showed abundant bcl-2 transcript, despite the absence of detectable bcl-2 protein. These results suggest that bcl-2 protein is broadly expressed in various hematopoietic neoplasms not restricted in t(14; 18) lymphomas and that germinal center cells may be involved in some arrest of bcl-2 protein expression at the posttranscriptional level.
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PMID:Detection of bcl-2 protein and bcl-2 messenger RNA in normal and neoplastic lymphoid tissues by immunohistochemistry and in situ hybridization. 139 59

Lymphoid neoplasms, like all malignant tumors, arise as a consequence of the accumulation, in a single cell, of a set of genetic lesions that result in altered proliferation or increased clonal life span. The most frequently observed genetic abnormalities among the malignant non-Hodgkin's lymphomas are translocations, which appear to be lineage and, to a large extent, lymphoma specific. Recombinases that normally mediate the process of antigen receptor gene rearrangement appear to have an important (but not exclusive) role in the mediation of these translocations and of other types of gene fusion (e.g., deletion of intervening DNA). Frequently, such fusions result in the increased or inappropriate expression of crucially important proteins, many of which are transcription factors that regulate the expression of other genes. These abnormalities, however, do not appear to be sufficient to induce lymphoma, and it is likely that the additional genetic lesions required differ from one tumor to another. The likelihood of any given clone of cells accumulating a sufficient number of relevant genetic lesions to give rise to a lymphoma is probably a function of its life span. Prolonged survival of a cell clone may be mediated by viral genomes (e.g., Epstein-Barr virus and human T-cell leukemia/lymphoma virus type 1), by the abnormal expression of cellular genes that inhibit apoptosis (e.g., bcl-2), or by the mutation or deletion of cellular genes that are necessary for apoptosis, e.g., p53. The background rate at which genetic lesions occur is amplified by the interaction of inherited and environmental factors, the latter appearing to be the major determinant of incidence rates. However, inherited factors that influence lymphomagenesis, including variability in the ability to repair DNA damage or in the fidelity of antigen receptor recombinases for their signal sequences, may be crucial determinants of which particular individuals in a given environmental setting develop lymphoma.
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PMID:Molecular basis of lymphomagenesis. 139 68

Characteristic gene rearrangements are present in most non-Hodgkin's lymphomas (NHL). These are usually detected by Southern blotting techniques. In this study, the ability of the polymerase chain reaction (PCR) to detect the t(14;18) chromosomal translocation and immunoglobulin heavy chain (IgH) gene rearrangement was evaluated. DNA from 14 follicular and 42 diffuse B-cell lymphomas was examined using oligonucleotide primers specific for opposing sides of the IgH gene rearrangement on chromosome 14 (towards conserved VH and JH sequences) and opposing sides of the t(14;18) chromosomal translocation (towards the major breakpoint region of the bcl-2 gene on chromosome 18 and conserved JH sequence on chromosome 14). The t(14;18) translocation was detected in 57% of follicular lymphomas and 21% of diffuse B-cell lymphomas. Clonal IgH gene rearrangements using PCR were detected in 50% follicular and 52% of the diffuse lymphomas. Either or both of these rearrangements were detected in 93% follicular and in 59% of diffuse lymphomas. PCR is a rapid and easy technique that can detect the abnormal rearrangement of the bcl-2 gene and clonal IgH rearrangement, indicating the presence of lymphoma. This may be of benefit in monitoring response to therapy and in predicting prognosis in this disease.
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PMID:The detection of specific gene rearrangements in non-Hodgkin's lymphoma using the polymerase chain reaction. 141 24

The B-cell lymphoma/leukemia oncogene bcl-2 takes part in crucial regulatory events in B-cell maturation and differentiation. The reciprocal chromosomal translocation t(14;18), leading to overexpression of this oncogene, can be found in the majority of follicular lymphomas and much less frequently in B-cell leukemias and diffuse lymphomas. We have studied the expression of this protein in different subtypes of Hodgkin's disease using monoclonal antibodies directed against a formalin-resistant epitope of the bcl-2 protein and also have investigated these cases by polymerase chain reaction for evidence of the t(14;18) translocation. We were particularly interested to determine whether nodular paragranuloma (lymphocyte-predominant, nodular), which differs from other subtypes of Hodgkin's disease by virtue of the B-cell nature of its malignant cell population, is characterized by expression of the bcl-2 protein. Our data indicate that only a small number of nodular paragranulomas express the bcl-2 protein and that the expression is not specific for this type of Hodgkin's disease. In a smaller number of cases this expression of bcl-2 could be explained by the presence of the translocation t(14;18).
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PMID:Expression of the bcl-2 oncogene product and chromosomal translocation t(14;18) in Hodgkin's disease. 142 49

Alternatives to Southern blot hybridization for gene rearrangement analysis are being studied because of the time, labor, cost, and radioisotopes required for this technique. We have utilized a rapid, hot air, thermocycling polymerase chain reaction (PCR) system to examine various lymphoproliferative disorders for immunoglobulin heavy chain (IgH) gene rearrangements. This unique system amplifies DNA from 10 microliters samples placed in glass capillary tubes, over a total cycle time of about 30 minutes. Amplified bands are easily visualized on ethidium bromide-stained agarose gels. Forty-one monoclonal B-cell proliferations, 27 reactive lymphoid hyperplasias, 17 T-cell lymphomas and 3 cases of Hodgkin's disease were studied. All 88 cases were fully characterized by morphologic, immunophenotypic, and genotypic (Southern blot) analyses. Each case was separately evaluated by PCR with two primer pairs: 1) IgH variable region (VH) and IgH joining region (JH) and 2) bcl-2 and JH. Thirty-four of 41 monoclonal B-cell proliferations revealed a distinct band (within an expected base pair range) with 1 or both primer combinations supporting B-cell monoclonality; the other 7 cases were considered false negatives. The 47 entities without IgH gene rearrangements detectable by Southern analysis demonstrated no amplified product or a smear of amplified DNA with no distinct band. The overall specificity of PCR was 100%, and the sensitivity was 83% when directly compared with Southern blot analysis. Although its sensitivity is currently less than optimal, PCR is a rapid and practical screening method for the detection of IgH gene rearrangements. If a positive result is obtained no further analysis is required; however, if there is a negative result, standard Southern blot analysis should be performed to definitively exclude the presence of a monoclonal B-cell population in the sample.
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PMID:Identification of monoclonal B-cell populations by rapid cycle polymerase chain reaction. A practical screening method for the detection of immunoglobulin gene rearrangements. 146 95


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