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

Reflecting the stepwise process of oncogenesis, lymphomas may cumulatively develop a more aggressive phenotype during the course of disease, a process referred to as lymphoma progression. Although morphological, clinical and biological aspects of lymphoma progression do not always overlap, changes in lymphoma morphology frequently indicate alterations in the clinical and biological behaviour of the disease. Indolent and aggressive lymphomas in disease progression can either be clonally related or represent clonally unrelated neoplasms. We propose to use the term 'lymphoma progression' in a biological sense denoting only clonal development of and within a lymphoma entity. The term 'composite lymphoma' should be used as a merely descriptive morphological designation for different lymphoma entities in one individual irrespective of clonal relationship. Many types of aggressive B-cell non-Hodgkin's lymphomas and Hodgkin's lymphomas are reported to secondarily develop in lymphoma progression. Genetic changes associated with lymphoma progression frequently abrogate the differentiating effects of alterations occurring in indolent lymphomas, leading to increased cell proliferation. Within different lymphoma entities, high-risk disease variants mimicking lymphoma progression exist.
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PMID:Pathology of lymphoma progression. 1131 94

Hodgkin and Reed-Sternberg (H&RS) cells are generally considered to be the neoplastic cells of Hodgkin's disease (HD); however, such H&RS cells are a few in number due to the numerous reactive cells. Very few data have so far been published on the cytogenetic abnormalities in HD. We have previously used the analysis of comparative genomic hybridization (CGH), employing sorted H&RS cells. The most commonly observed genetic aberrations were a loss on 16q11/21, a gain on 1p13 and a gain on 7q35/36. To confirm the loss of 16q, we analyzed the loss of heterozygosity (LOH) using the regions D16S3075 (16p13), D16S3068 (16q11), D16S3136 (16q12), D16S503 (16q13), D16S515 (16q21), D16S3091 (16q23) and D16S520 (16q24). A total of 100 sorted H&RS cells were compared with a similar number of sorted reactive T cells in 15 cases with HD, including 5 cases with nodular sclerosis (NS) type and 10 cases with mixed cellularity (MC) type. LOHs of 16q, especially 16q21-23, were frequently detected, but 16p deletions were infrequent. Analysis of 16q21 showed LOH in 12 of 15 cases with HD (80%), including 9 cases with MC type (90%) and 3 cases with NS type (60%). 16q23 showed LOH in 9 of 15 cases with HD (60%), including 5 cases with MC type (50%) and 4 cases with NS (80%). On the other hand, 16p13 showed LOH in 3 of 15 cases with HD (20%). Immunohistochemical staining showed that H&RS cells rarely expressed E-cadherin, which is located on 16q. Our findings suggest that 16q deletion, especially 16q21-23, is probably involved in H&RS giant cell formation and tumorigenesis.
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PMID:Chromosome 16q deletion and loss of E-cadherin expression in Hodgkin and Reed-Sternberg cells. 1134 May 71

Patients with Nijmegen breakage syndrome (NBS) have a high risk to develop malignant diseases, most frequently B-cell lymphomas. The NBS gene product, nibrin, is involved in DNA recombination repair, a function shared with known tumor suppressor genes like BRCA1 and BRCA2. This led us to investigate whether NBS acts as tumor suppressor gene in the development of non-Hodgkin lymphomas. Therefore, we performed fluorescence in situ hybridization analysis using a BAC clone containing the entire NBS1 region on eight B-cell and eight T-cell lymphomas, including one B-cell and two T-cell lymphomas with structural abnormalities of 8q. None of the tumors showed a deletion of the NBS1 gene, demonstrating that deletion of the NBS1 gene is not a major cause or a primary event in tumorigenesis of human B- and T-cell lymphomas.
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PMID:No evidence for deletions of the NBS1 gene in lymphomas. 1134 81

Telomerase, an enzyme associated with cellular immortality, is expressed on malignant tumor cells. Deregulation of telomerase is thought to facilitate tumorigenesis and cellular immortality by providing cancer cells with unlimited proliferation capacity. Hodgkin and Reed-Sternberg (H&RS) cells are generally considered as neoplastic cells in Hodgkin's disease (HD), however, such cells are only found in a minority of HD lesions. In addition, H&RS cells with mitotic features are rare and mummified forms are occasionally encountered. There are no available data on the relationship between telomerase activity and apoptosis in HD. We studied 14 cases with Hodgkin's disease (mixed cellularity type, nine cases; nodular sclerosis type, five cases) to clarify the relationship between telomerase activity and apoptosis using in situ hybridization of human telomerase reverse transcriptase (hTERT), reverse transcriptase-polymerase chain reaction (RT-PCR) of hTERT, using extracted RNA and immunohistochemistry of nuclear factor-?B (NF-?B), and TdT-mediated dUTP-digoxigenin nick end-labeling (TUNEL) technique for apoptosis. We also analyzed the telomere length, using sorted H&RS cells. TUNEL showed a few apoptotic H&RS cells, but the cells frequently expressed hTERT, as confirmed by ISH and RT-PCR. Lengthening of the telomere of H&RS cells was noted in ten cases. In addition, H&RS cells frequently expressed NF-?B, which is known as an inducible transcription factor and inhibitor of apoptosis. Our findings of telomerase activity in H&RS cells indicate that these cells are neoplastic and are potentially immortal. In addition, NF-?B expression on H&RS cells suggests its possibility in inhibition of apoptosis of these cells.
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PMID:Possible immortalization of Hodgkin and Reed-Sternberg cells: telomerase expression, lengthening of telomere, and inhibition of apoptosis by NF-kappaB expression. 1137 50

Translational control is an important but relatively unappreciated mechanism that regulates levels of protein products. In addition to a global translational control that regulates the cell's response to external stimuli such as growth factors, cytokines, stress and viral infections, selective translational control has recently been demonstrated to affect many genes related to growth and apoptotic processes. Modifications in the 5'untranslated region of these specific mRNAs may lead to an up-regulation of the protein product by as much as 100-fold. Translational infidelity has been reported in some human cancers for oncogenes such as c-myc and mdm2. Furthermore, modulation of selective translational control has also been demonstrated in cells over-expressing the translation initiation factor elF4E. Elevated levels of elF4E were found in a broad spectrum of solid tumors (breast, head and neck, colon and bladder carcinomas as well as in non-Hodgkin's lymphomas). Other translation initiation factors and translation components such as elongation factors and ribosomal proteins have also been reported to be overexpressed in some human tumors. This review discusses the relevance of these observations to a cell's proteome and for tumorigenesis and how the genomics and proteomics can be used to advance our understanding of the role of translational control in cancer.
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PMID:Translational control of the proteome: relevance to cancer. 1172 31

Most lymphoid malignancies are initiated by specific chromosomal translocations between immunoglobulin (Ig)/T cell receptor (TCR) gene segments and cellular proto-oncogenes. In many cases, illegitimate V(D)J recombination has been proposed to be involved in the translocation process, but this has never been functionally established. Using extra-chromosomal recombination assays, we determined the ability of several proto-oncogenes to target V(D)J recombination, and assessed the impact of their recombinogenic potential on translocation rates in vivo. Our data support the involvement of 2 distinct mechanisms: translocations involving LMO2, TAL2, and TAL1 in T cell acute lymphoblastic leukemia (T-ALL), are compatible with illegitimate V(D)J recombination between a TCR locus and a proto-oncogene locus bearing a fortuitous but functional recombination site (type 1); in contrast, translocations involving BCL1 and BCL2 in B cell non-Hodgkin's lymphomas (B-NHL), are compatible with a process in which only the IgH locus breaks are mediated by V(D)J recombination (type 2). Most importantly, we show that the t(11;14)(p13;q32) translocation involving LMO2 is present at strikingly high frequency in normal human thymus, and that the recombinogenic potential conferred by the LMO2 cryptic site is directly predictive of the in vivo level of translocation at that locus. These findings provide new insights into the regulation forces acting upon genomic instability in B and T cell tumorigenesis.
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PMID:V(D)J-mediated translocations in lymphoid neoplasms: a functional assessment of genomic instability by cryptic sites. 1178 68

Histochemical stains demonstrate Epstein-Barr virus (EBV) in approximately 40% of all Hodgkin hymphomas, suggesting a role in tumorigenesis and the potentialfor EBV-targeted therapy. As research progresses, it is important to define criteria for interpreting histochemical stains. Four hematopathologists independently interpreted EBV-encoded RNA (EBER) and latent membrane protein 1 (LMP1) histochemical stains from 40 cases of Hodgkin lymphoma and then reviewed the stains as a group to resolve discrepancies and to develop interpretation guidelines. To call a Hodgkin case EBV-related, the EBER and/or LMP1 signal must be unequivocally present in Reed-Sternberg/Hodgkin (RS/H) cells. The cytologic features and distribution of stained cells should be matched with those on the corresponding H&E-stained slide to help interpret whether the EBER or LMP1 signal is in malignant or reactive cells. The EBER signal is localized to the nucleus, whereas LMP1 is in the cytoplasm and surface membrane. In some cases, only a fraction of RS/H cells express these factors for technical or biologic reasons. Before calling a case EBER-negative, it is essential to show that tumor cell RNA is preserved and available for hybridization. LMP1 staining, although usually strong among all tumor cells in a given case, may alternatively be focal and weak, contributing to false-negative interpretation. EBER and LMP1 assays in combination are more effective than either assay alone for identifying EBV-related Hodgkin lymphoma.
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PMID:Guidelines for interpreting EBER in situ hybridization and LMP1 immunohistochemical tests for detecting Epstein-Barr virus in Hodgkin lymphoma. 1186 22

This study assessed the changes in the isoprenoid pathway and its metabolites digoxin, dolichol and ubiquinone in neoplasms (CNS astrocytomas - glioblastoma multiforme and high grade non - Hodgkin's lymphoma). The following parameters were assessed-isoprenoid pathway metabolites, tyrosine and tryptophan catabolites, glycoconjugate metabolism, RBC membrane composition and free radical metabolism. There was an elevation in plasma HMG CoA reductase activity, serum digoxin and dolichol and a reduction in RBC membrane Na+-K+ ATPase activity, serum ubiquinone and magnesium levels. Serum tryptophan, serotonin, nicotine and quinolinic acid were elevated while tyrosine, dopamine, noradrenaline and morphine were decreased. The total serum glycosaminoglycans and glycosaminoglycan fractions (except dermatan sulphate in the case of CNS astrocytomas), the activity of GAG degrading enzymes and glycohydrolases, carbohydrate residues of glycoproteins and serum glycolipids were elevated. HDL cholesterol showed a significant decrease and free fatty acids & triglycerides were increased. The RBC membrane glycosaminoglycans, hexose and fucose residues of glycoproteins and phospholipids were reduced. The activity of all free radical scavenging enzymes, concentration of glutathione, iron binding capacity and ceruloplasmin decreased significantly while the concentration of malondialdehyde (MDA), hydroperoxides, conjugated dienes and NO increased. The concentration of alpha tocopherol was unaltered. Membrane Na+-K+ ATPase inhibition due to elevated digoxin, altered membrane structure and digoxin related tyrosine / tryptophan transport defect leading to increased levels of depolarising tryptophan catabolites and decreased levels of hyperpolarising tyrosine catabolites can lead to alteration in intracellular calcium/magnesium ratios and oncogene activation. Intracellular magnesium deficiency can produce defective microtubule related spindle fibre dysfunction and chromosomal non-dysjunction contributing to neoplastic cellular polyploidy and aneuploidy. Digoxin induced tryptophan/tyrosine transport defect can alter neurotransmitter patterns with increased serotonin, quinolinic acid, nicotine & glutamatergic transmission and reduced dopamine, morphine and noradrenaline levels leading to oncogenesis. Glycoconjugate metabolism is altered by elevated dolichol levels and magnesium depletion consequent to Na+-K+ ATPase inhibition. There is a qualitative alteration in proteoglycans and glycoproteins, defective membrane formation and structure and reduced lysosomal stability leading to disordered contact inhibition and tumour antigen presentation contributing to oncogenesis. Digoxin induced alteration in intracellular calcium/magnesium ratios and low ubiquinone levels can lead to a mitochondrial dysfunction resulting in increased free radical generation and reduced scavenging & caspase-3 activation producing a P21 defect contributing to oncogenesis.
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PMID:Hypothalamic digoxin mediated model for oncogenesis. 1187 54

Epstein-Barr virus (EBV) is frequently detected in haematological malignancies, including Burkitt's lymphomas/leukaemias, Hodgkin's diseases and non-Hodgkin's lymphomas. However, immature T-cell malignancies associated with EBV have not been reported previously. We report a patient with T-cell acute lymphoblastic leukaemia (T-ALL), whose leukaemic cells had EBV, confirmed by Southern blotting and in situ hybridization. The EBV existed in episomal form and was detected in most leukaemic cells, but not in bystander normal B-cells. The leukaemic cells, massively infiltrated into the liver and spleen, were resistant to chemotherapy. EBV might be associated with tumorigenesis of T-ALL, and characteristic clinical features of the patient.
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PMID:Epstein-Barr virus-associated T-cell acute lymphoblastic leukaemia. 1191 42

Notch signaling controls cell fate decisions of hematopoietic progenitors by inhibiting certain steps of differentiation and inducing either self-renewal or differentiation toward lymphoid or myeloid lineages. In addition, truncated Notch1 alleles could be associated with 10% of all cases of human T lymphoblastic leukemia and, when introduced into mouse bone marrow stem cells, cause T-cell neoplasms. However, functional links between the abundant expression of intact Notch1 and oncogenesis are still lacking. Here we show that Notch1 is highly expressed in B- and T-cell-derived tumor cells of Hodgkin and anaplastic large cell lymphoma. We demonstrate a novel mechanism for the oncogenic capacity of Notch1 by showing that the interaction between intact Notch1 on tumor cells and its ligand Jagged1 dramatically induces proliferation and inhibition of apoptosis in vitro. We further provide evidence that in Hodgkin and anaplastic large cell lymphoma, Jagged1 is expressed in malignant and in bystander cells colocalizing with Notch1-positive tumor cells. Notch1 signaling may therefore be activated in tumor cells by Jagged1 through homotypic or heterotypic cell-cell interactions, and it seems likely that these interactions contribute to lymphomagenesis in vivo. Thus, our data suggest that activated Notch1 signaling plays an important role in the pathobiology of Hodgkin and anaplastic large cell lymphoma and that it might be a potential new target for treatment.
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PMID:Activated Notch1 signaling promotes tumor cell proliferation and survival in Hodgkin and anaplastic large cell lymphoma. 1196 9


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