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)

The mechanism by which PG of the E series (PGE) promote murine B lymphocyte IgE production was investigated. We previously reported that PGE, and other agents that increase intracellular cAMP, synergize with IL-4 and LPS to induce IgE and IgG1 production while inhibiting IgM and IgG3 synthesis. These data suggested that PGE may promote IL-4-induced class switching, but the mechanism by which PGE increases IgE synthesis remained obscure. We report here that 1) PGE increases (up to 14-fold) the number of splenic B cells secreting IgE, even though PGE mildly inhibits proliferation. 2) PGE acts on sorted surface IgM positive B cells, consistent with PGE acting on uncommitted B cells to promote class switching to IgE. 3) PGE synergizes with IL-4 to induce germline epsilon transcripts, demonstrating that PGE acts at the level of transcription in cells that have not yet switched to IgE. 4) In the presence of PGE, rearranged mature V(D)J epsilon mRNA transcripts can be detected earlier and at higher levels than with IL-4 and LPS alone. Taken together, these data provide strong evidence that PGE synergizes with IL-4 and LPS to direct isotype switching to the epsilon heavy chain gene in purified B lymphocytes. PGE is a potentially important in vivo immunoregulator, particularly with regard to IgE production and the genesis of allergy. In support of this hypothesis, there are numerous clinical conditions (hyper-IgE, trauma, sepsis, Hodgkin's lymphoma, arthritis) in which overproduction of PGE is coincident with elevated IgE titers.
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PMID:Prostaglandin E2 promotes B lymphocyte Ig isotype switching to IgE. 799 35

The t(14;19)(q32;q13) is a recurring translocation found in some patients with chronic lymphocytic leukemia (CLL), and the t(14;19) juxtaposes the BCL3 gene on chromosome 19 with the immunoglobulin heavy chain gene (IGH) locus on chromosome 14. Genomic DNAs from 49 patients with chronic B-cell leukemia and the related lymphomas were examined by Southern blot hybridization using 2 separate probes, named p alpha 1.4P and p alpha .5B, from the BCL3 gene locus. None of the 18 patients with leukemic manifestations of non-Hodgkin's lymphomas had detectable BCL3 rearrangements. Of 31 patients with CLL, 2 had the BCL3 rearrangements. A comigration study using the C alpha and C epsilon constant gene probe from IGH indicated that the t(14;19) translocation occurred in these 2 patients, and they were diagnosed with CLL/prolymphocytic (PL) according to the French-American-British (FAB) classification. Probes for the IGH locus revealed that leukemia cells of the 2 patients each were clonal, indicating that both small lymphocytes and prolymphocytoid cells found in the peripheral blood of one patient had the t(14;19), as well as a major population of the small lymphocytes in the peripheral blood of a second patient. It thus appears that tumor cells carrying the t(14;19) constitute a distinct disease entity in a group of chronic B-cell leukemia, that has a converting potential to more aggressive forms.
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PMID:Involvement of the BCL3 gene in two patients with chronic lymphocytic leukemia. 801 90

The interchromosomal 14;18 translocation occurs in approximately 70-80% of follicular lymphomas and in a lower proportion of high-grade non-Hodgkin lymphomas of the lymph nodes. This translocation results in the fusion of the bcl-2 oncogene on chromosome 18 with immunoglobulin heavy chain genes on chromosome 14, and in the expression of higher amounts of normal bcl-2 protein. We studied bcl-2 expression in biopsies of 108 patients with benign and malignant cutaneous lymphoproliferative diseases (B-cell lymphoma, primary cutaneous, 42; secondary cutaneous, 21; primary cutaneous T-cell lymphoma, 21; B-cell pseudolymphoma, 24), using a monoclonal anti-bcl-2 antibody on paraffin-embedded tissue sections, bcl-2 protein was detected immunohistochemically in 16 of 63 cases of cutaneous B-cell lymphoma, whereas cutaneous T-cell lymphomas and B-cell pseudolymphomas were negative. The proportion of bcl-2 protein expression was significantly higher in secondary (11/21) than in primary cutaneous B-cell lymphomas (5/42; chi 2 test, p < 0.001). Biopsies from 25 of these patients (B-cell lymphoma, 22; B-cell pseudolymphoma, three) were analyzed previously on the molecular level for the t(14;18), using polymerase chain reaction amplification of DNA obtained from paraffin-embedded sections. In four of 11 cases of bcl-2 protein-positive B-cell lymphoma (primary, one; secondary, three) the t(14;18) was detected by polymerase chain reaction. All other cases of B-cell lymphoma, including seven cases where bcl-2 protein was detected by immunohistology, and B-cell pseudolymphoma were negative. These results demonstrate: 1) bcl-2 protein is expressed in a small portion of cutaneous B-cell lymphomas; 2) bcl-2 protein expression is significantly more frequent in secondary than in primary cutaneous B-cell lymphoma; 3) only approximately one-third of cases expressing the bcl-2 protein are characterized also by the t(14;18). bcl-2 protein expression might indicate that the cutaneous manifestation of the lymphoma represents a secondary spread from a node-based lymphoma.
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PMID:bcl-2 protein expression and correlation with the interchromosomal 14;18 translocation in cutaneous lymphomas and pseudolymphomas. 810 52

To determine whether correlations existed between morphologic and immunophenotypic findings and clinical characteristics, 30 cases of T-cell-rich large B-cell lymphomas (TBL) were evaluated by histopathology, immunostaining, and polymerase chain reaction on paraffin-embedded material. All were characterized by a polymorphic cell composition, including a variable mixture of small and large lymphoid cells and reactive cell. Most cases (87%) fitted into one of three main histologic types of non-Hodgkin's lymphoma (diffuse, mixed cell; diffuse, large cell; follicular and diffuse, mixed cell), and one group of eight cases had the prototypic features described by Ramsay et al. (17). All cases showed a component of large CD20(L26)+ MB2+ B cells in a predominant back-ground of reactive T cells (> 50% of the total lymphoid forms). Clonality was demonstrated by light chain restriction in 67% of cases and by rearrangement of the immunoglobulin heavy chain gene and bcl-2 gene in 64% and 28% of cases, respectively. The patients were predominantly men (70%), ages 18-83 years (median of 62.5), and were initially seen predominantly with nodal disease (and extranodal involvement in 20%) at advanced stages (III-IV: 77%). Treatment was mostly aggressive chemotherapy, and the outcomes were favorable (84% alive and well). These features are not distinctive as compared with those of typical large-cell lymphoma, nor did subgroups within the series (prototypic cases versus others; cases with less [< or = 70%] or more [> 70%] T-cell infiltration) significantly differ in clinical presentation or outcome. Thus, this study confirms that TBL, while useful as a diagnostic variant to be distinguished from both peripheral T-cell lymphoma and Hodgkin's disease, is a heterogeneous assortment of diverse histopathologic categories rather than a clinicopathologic entity. The term "T-cell rich" might, however, be usefully retained as a morphologic specification to be added to recognized histologic categories of lymphoma.
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PMID:T-cell-rich large B-cell lymphoma. A study of 30 cases, supporting its histologic heterogeneity and lack of clinical distinctiveness. 779 83

Centrocytic lymphoma (CC) and intermediately differentiated lymphocytic lymphoma (IDL) are B-cell non-Hodgkin's lymphomas composed of lymphocytes presumably derived from follicle mantle cells. In these lymphomas, a specific chromosomal translocation, t(11;14)(q13;q32), has been described. Previous studies suggested an association between t(11;14) chromosomal translocations and BCL-1 rearrangements. To evaluate the association between BCL-1 rearrangements and CC/IDL, Southern blot analysis was performed on a panel of 20 cases of CC/IDL, 22 cases of morphologically similar non-Hodgkin's lymphomas, 11 cases of chronic B-cell leukemias, and 2 cases of myelomas. We used various probes covering a considerable proportion of the 120-kilobase BCL-1 locus, and rearrangements in 50% of CC/IDL (10 of 20) were detected. In CC, all 4 breakpoints were located at the major translocation cluster (MTC). In contrast, in IDL, rearrangements were detected in 3 different cluster regions: 2 cases in the MTC, 2 cases with a breakpoint 24 kilobases outside the MTC, and 2 additional cases with breakpoints found 3 kilobases 5' of the first exon of the PRAD1/CCND1 gene, which is located 120 kilobases outside the MTC. In addition, one leukemia showed a breakpoint 63 kilobases outside the MTC. In all cases, there was comigration of the rearranged 11q13 fragment and the immunoglobulin heavy chain-joining gene complex, indicating a t(11;14)(q13;q32) chromosomal rearrangement. Our results show that Southern blot analysis is helpful to identify CC/IDL, but multiple breakpoints are present over a large region, and therefore, many probes are necessary to cover all breakpoints.
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PMID:Multiple breakpoints within the BCL-1 locus in B-cell lymphoma: rearrangements of the cyclin D1 gene. 836 7

The recombination activating gene, RAG-1, which is supposed to encode a molecule regulating V(D)J recombination, has been isolated. In the current study, the distribution of RAG-1 expression in human neoplastic hematopoietic cells was compared with the phenotypic and genotypic status of differentiation. Thirty-one hematopoietic cell lines (16 B-lineage, 9 T-lineage, 2 Hodgkin's disease, and 4 nonlymphoid cell lines) were investigated for the expression of human RAG-1 using the reverse-transcriptase polymerase chain reaction (RT-PCR). RAG-1 was not expressed in nonlymphoid, Hodgkin's disease, or mature-stage lymphoid cell lines, but was present in some acute lymphoblastic leukemia (ALL)/lymphoblastic lymphoma (LBL) cell lines. The investigation was extended to 45 cases of fresh ALL/LBL cells. The patterns of RAG-1 expression found in the cell lines and fresh ALL/LBL cells were similar. In B-lineage cells, the product of RAG-1 RT-PCR was detected in CD19+ CD10- CD20- CD5- stage (stage II, Nadler's classification) and was at the highest level in CD19+ CD10+ CD20- CD5- stage (stage III), but was absent or limited in CD19+ CD10+ CD20-+ CD5- (stage IV) or CD19+ CD10+ (or CD10-) CD5+. In stage II, monoclonal gene rearrangements of only the immunoglobulin heavy chain (IgH) were found, whereas monoclonal gene rearrangements of both IgH and T-cell receptor (TCR)-beta chain were frequently noted in stages III and IV. The expression of CD20 or CD5 antigen apparently correlated with the decline of RAG-1 expression. In T-lineage cells, RAG-1 was highly expressed in CD3- CD4+ CD8+/CD3+ CD4+ CD8+ thymic stages, but was negative or only weakly expressed in the CD3- CD4- CD8- prothymic or early thymic stage, in which the TCR-beta gene was often germline, or the CD3+ CD4+ CD8- mature thymic stage. The relative levels of RAG-1 mRNA give an additional delineating frame to the schemes of lymphoid differentiation based on phenotypic and genotypic status. RAG-1 is exhibited by cells of the thymic stage capable of synthesizing TCR or expressing it on the cell surface. The weak or absent expression of RAG-1 in the prothymic or early thymic stage suggests that the contribution of RAG-1 to the gene rearrangement may differ quantitatively between TCR-delta/TCR-gamma and TCR-beta.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Human recombination activating gene-1 in leukemia/lymphoma cells: expression depends on stage of lymphoid differentiation defined by phenotype and genotype. 839 73

We examined 81 cases of Hodgkin's disease for evidence of the t(14;18) translocation, using the polymerase chain reaction assay on lysates of formalin-fixed, paraffin-embedded tissue. Seven of 74 amplifiable cases (9%) were positive for the translocation, which involves the bcl-2 oncogene and the immunoglobulin heavy chain gene. Two of these cases were sequenced and the breakpoints had the same pattern found in follicular lymphoma. The nuclei from one of the cases were sorted into large and small subpopulations. The t(14;18) signal was more intense in the large nucleus subpopulation, which contained a greater proportion of Reed-Sternberg-like nuclei. These results are consistent with the hypothesis that Reed-Sternberg cells carry the translocation, but they do not exclude the possibility that the translocation is found in cells representing the reactive component of Hodgkin's disease. The results also demonstrate that routinely processed material is suitable for polymerase chain reaction-based analysis of translocations, although the sensitivity is reduced 10- to 100-fold, compared with fresh tissue.
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PMID:bcl-2 rearrangement in Hodgkin's disease. Results of polymerase chain reaction, flow cytometry, and sequencing on formalin-fixed, paraffin-embedded tissue. 843 38

Chromosomal translocations involving chromosome 3, band q27, are among the most common rearrangements in B-cell non-Hodgkin lymphoma. From a bacteriophage lambda library prepared from a lymphoma characterized by a t(3;14)(q27;q32), genomic clones were isolated using a probe from the immunoglobulin heavy chain locus (IGH) joining region. In addition to clones containing an apparently normal IGH rearrangement, others were found to contain one of the translocation breakpoint junctions. Normal chromosome 3 sequences and the reciprocal breakpoint junction were subsequently isolated. DNA probes on each side of the chromosome 3 breakpoint hybridized at high stringency to the DNA of various mammalian species, demonstrating evolutionary conservation. One such probe from the presumptive der(3) chromosome detected an 11-kilobase transcript when hybridized to RNA of B- and T-cell lines. A probe made from partial cDNA clones isolated from a T-cell line hybridized with genomic DNA from both sides of the chromosome 3 breakpoint, indicating that the t(3;14) is associated with a break within the gene on chromosome 3. In situ chromosomal hybridization revealed that the same gene is involved in the t(3;22)(q27;q11). Preliminary nucleotide sequencing shows no identity of the cDNA to gene sequences in available data banks. We propose the name BCL6 (B-cell lymphoma 6) for this gene, since it is likely to play a role in the pathogenesis of certain B-cell lymphomas.
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PMID:Identification of the gene associated with the recurring chromosomal translocations t(3;14)(q27;q32) and t(3;22)(q27;q11) in B-cell lymphomas. 850 75

The bcl-2 gene is rearranged in most cases of follicular lymphoma and the breakpoint clusters into two specific regions: mbr and mcr. Rearrangements to immunoglobulin heavy chain genes (IgH) result in a deregulation of the gene and increased transcription of mRNA for the bcl-2 protein. In chronic lymphocytic leukaemia (CLL) expression of bcl-2 protein is increased but rearrangement of the gene can be found only in a minority of cases: commonly a variant translocation with a breakpoint region located 5' of the bcl-2 gene (vcr) with preferential rearrangement to immunoglobulin light chain genes. We have analysed breakpoints in mbr and vcr in malignant cells from 96 patients with B-CLL, 45 with hairy cell leukaemia (HCL) and 41 with high- and low-grade non-Hodgkin's lymphomas (NHL). Vcr rearrangements were observed in nine patients (12%) with B-CLL. Four patients had co-migration of rearranged bcl-2 bands to kappa genes and two patients to IgH. Cytogenetic abnormalities involving 18q21, the site of the bcl-2 gene, was found in two cases only. In several cases with bcl-2 gene rearrangement chromosomal aberrations not including 18q21 were observed. In six patients (two B-CLL, one follicular lymphoma, one immunocytoma and two high-grade lymphomas), breakpoints in both vcr and mbr were found. In HCL a rearrangement in the vcr region was found in one case. Bcl-2 protein immunostaining of B-CLL showed intense bcl-2 expression in all cases and no correlation was found between gene rearrangement and protein expression. Our study confirms that breakpoints in the bcl-2 gene commonly cluster to the vcr region in B-CLL, but in most cases over-expression of bcl-2 protein has to be explained by other mechanisms than bcl-2 gene rearrangement. We also report that simultaneous breakpoints in mbr and vcr is a recurrent phenomenon in B-CLL and in other high- and low-grade non-Hodgkin's lymphomas.
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PMID:Bcl-2 rearrangements with breakpoints in both vcr and mbr in non-Hodgkin's lymphomas and chronic lymphocytic leukaemia. 861 30

The chromosomal aberration t(2:5) resulting in the juxtaposition of NPM and ALK genes is a well-known feature of several Ki-1+ anaplastic large cell lymphomas (ALCL) of the T-cell type. However, conflicting results have been reported concerning the presence of this gene rearrangement in other ALCL and Hodgkin's disease (HD), respectively. We performed NPM/ALK RT-PCR on 14 cases of ALCL expressing distinct myelomonocytic markers, e.g. CD11c, CD13, CD14 or CD68, but neither T-cell nor B-cell associated antigens (null cell phenotype). The specific translocation was found exclusively in six childhood tumours previously diagnosed as malignant histiocytosis (MH), whereas all adult lymphomas (three ALCL without characteristics of MH, three secondary ALCL following HD) and two paediatric cases of secondary ALCL following HD did not show NPM/ALK gene fusion products. By Southern blotting, the status of T-cell receptor (TCR) and immunoglobulin heavy chain genes (IgH) were investigated; two patients with initially diagnosed MH had the TCRdelta-chain gene rearranged (Ddelta2-Ddelta3 and Vdelta1-Jdelta1, respectively). IgH rearrangements were detected in only one patient with secondary ALCL. Our data indicate a high association of previously diagnosed MH and NPM/ALK gene rearrangements. In one case, this specific translocation was demonstrated at an early stage of development; in another, a mature TCRdelta-chain gene rearrangement was detected. These data support the hypothesis of a lymphoid origin of this subgroup of Ki-1 positive ALCL previously diagnosed as MH.
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PMID:NPM/ALK gene fusion transcripts identify a distinct subgroup of null type Ki-1 positive anaplastic large cell lymphomas. 861 79


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