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 precise cellular origin and the pathogenetic mechanism(s) leading to the neoplastic transformation of anaplastic large cell lymphoma (ALCL) and the Reed-Sternberg cell of Hodgkin's disease (HD) remains largely uncertain. Classical cytogenetic analysis has shown a unique translocation involving bands 2p23 and 5q35 bands in a variable number of ALCLs. It has been recently shown that the nucleophosmin/B23 (NPM) gene (5q35) and a novel anaplastic lymphoma kinase (ALK; 2p23) are the fused genes of t(2;5). To investigate the presence and the precise frequency of NPM-ALK gene products among ALCL and HD cases, a large and well-characterized panel of ALCL (n = 49) and HD (n = 72) cases was studied using multiple strategies including reverse transcriptase-polymerase chain reaction (RT-PCR), Southern blot analysis, and immunohistochemistry. Overall, 6 (3 T and 3 null) of 49 ALCL and 3 (2 nodular sclerosis and 1 mixed cellularity) of 72 HD showed the presence of NPM-ALK transcripts by RT-PCR. NPM-ALK gene rearrangements were detected in all RT-PCR, NPM-ALK-positive ALCL by Southern blot analysis. Furthermore, in all the available cases we were able to show the presence of ALK-related protein using a specific polyclonal antiserum recognizing the cytoplasmic domain of ALK by immunohistochemistry. Our data show that NPM-ALK gene transcripts are identified in a subpopulation of ALCL, almost exclusively in T or null cell in origin, and in rare cases of HD. These findings show that some HD may be closely related to ALCL, giving us new insights on the pathogenesis and possibly biologic evolution of HD.
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PMID:Molecular characterization of the t(2;5) (p23; q35) translocation in anaplastic large cell lymphoma (Ki-1) and Hodgkin's disease. 856 33

There is now considerable evidence suggesting that alterations in the DNA methylating machinery play an important role in tumorigenesis and tumour progression. For example, focal hypermethylation and generalised genomic demethylation are features of many different types of neoplasms. It is thought that tumorigenesis and tumour progression may be caused by hypermethylation induced mutational events and silencing of genes which control cellular proliferation and/or demethylation induced reactivation of genes which may only be required during embryological development. Consequently, we have begun to investigate the role of DNA methylation and developmental genes in malignant lymphoproliferative diseases. Previously, in all cases of non-Hodgkins lymphoma and leukemia studied, we have shown that the myogenic developmental gene Myf-3 is abnormally hypermethylated. In this review we discuss the possible significance of these findings since in vitro studies suggest that Myf-3 may play an important role in control of the cell cycle and therefore lymphomagenesis. In vitro and in vivo evidence suggests that PAX genes may also have oncogenic potential. The PAX family of developmental genes are involved in cellular differentiation, proliferation and cell migration. Expression of PAX3 in particular is associated with cellular mobility. Our previous studies have indicated that alternate regional expression of PAX genes may be controlled by DNA methylation. Therefore, we have proposed that abnormal methylation profiles of PAX3 may be associated with neoplastic transformation and/or metastatic potential. Results thus far reveal that the paired box of PAX3 is abnormally hypermethylated and the homeobox abnormally hypomethylated in lymphomas and leukemias. These new findings are consistent with our postulate and support the idea that inappropriate methylation induced activation or inactivation of developmental genes such as Myf-3 and PAX3 play an important role in lymphomagenesis and disease progression and that inspection of the methylation status of other developmental genes is warranted.
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PMID:DNA methylation and developmental genes in lymphomagenesis--more questions than answers? 915 51

CD44 is a family of transmembrane glycoproteins that act mainly as a receptor for hyaluronan. It can also bind some other extracellular matrix ligands (chondroitin sulphate, heparan sulphate, fibronectin, serglycin, osteopontin) with lower affinity. CD44 is encoded by a single gene containing 20 exons, 10 of which (v1-v10) are variant exons inserted by alternative splicing. The standard, ubiquitously expressed isoform of CD44, does not contain sequences encoded by these variant exons. Numerous variant isoforms of CD44 containing different combinations of exons v1-v10 inserted into the extracellular domain can be expressed in proliferating epithelial cells and activated lymphocytes. CD44 plays a significant role in lymphocyte homing. Both alternative splicing and glycosylation influence receptor function of the molecule, usually reducing its affinity to hyaluronan. The cytoplasmic domain of CD44 communicates with the cytoskeleton via ankyrin and proteins belonging to the ezrin-moesin-radixin family. Relatively little is known about the intracellular events following interactions of CD44 with its ligands. Some variant isoforms, especially those containing sequences encoded by v6-v10, are overexpressed in both human and animal neoplasms. In a rat pancreatic adenocarcinoma model one of the variant CD44 isoforms was proved to be determinant in the metastatic process. For some human neoplasms (carcinomas of the digestive tract, non-Hodgkin's lymphomas, thyroid carcinomas, and others) correlations have been made between the particular pattern of CD44 variants produced by neoplastic cells and clinicopathological parameters of tumours, such as grade, stage, presence of metastases, and survival. In vitro studies indicate that modifications of CD44 expression result in different ligand recognition and influence cell motility, invasive properties, and metastatic potential of experimental tumours. Investigation of CD44 neoexpression can be useful both in early cancer diagnosis and in predicting tumour behaviour. It can also contribute to better understanding of molecular mechanisms leading to neoplastic transformation.
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PMID:CD44 and the adhesion of neoplastic cells. 923 Nov 52

The expression pattern of the BCL-6 transcription factor has been assessed in normal and neoplastic B-cell populations and in Hodgkin's disease. However, little is known about BCL-6 expression and its biological significance in T-cell neoplasms. In this study, a series of 59 lymphoma samples, including 27 CD30+ anaplastic large-cell lymphomas (ALCLs), 24 other peripheral T-cell neoplasms, and 8 T-cell lymphoblastic lymphomas (T-LBLs), as well as a panel of t(2;5)-positive lymphoma-derived human cell lines, were evaluated for BCL-6 protein expression by immunohistochemistry on frozen sections and cell smears. To define the relationship between BCL-6 protein and CD30 antigen in CD30+ ALCLs and in non-neoplastic lymph nodes, serial section immunohistochemistry and two-color staining were used in selected CD30+ ALCLs as well as in reactive lymph nodes with non-neoplastic T-cell proliferations. BCL-6 protein was expressed in 12 of 27 (45%) CD30+ ALCL cases, irrespective of their antigenic phenotypes (T-cell or null-cell type), and in the t(2;5)-positive cell lines. In contrast, the remaining 24 peripheral T-cell neoplasms as well as the 8 T-LBLs were considered negative for BCL-6 expression. Coexpression of CD30 and BCL-6, as detected in CD30+ ALCLs, was also found in a subset of non-neoplastic lymphoid elements, namely the large lymphoid cells scattered in the interfollicular areas of reactive lymph nodes. These findings suggest that CD30+ ALCLs may represent the neoplastic transformation of extrafollicular CD30+ cells and that BCL-6 may provide an additional marker for characterizing CD30+ ALCLs.
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PMID:BCL-6 protein expression in human peripheral T-cell neoplasms is restricted to CD30+ anaplastic large-cell lymphomas. 931 Apr 96

This review highlights three topics in which major contributions to lymphoma biology have recently been achieved. First, the use of single-cell polymerase chain reaction analysis has allowed for a better understanding of the origin of several entities, eg, Hodgkin's, Burkitt's, and marginal zone B-cell lymphomas. Second, the studies of mechanisms regulating apoptosis and survival of the neoplastic clones have opened a whole area of research with promising expectations for new therapeutical approaches. Finally, the recent cloning of genes involved in several chromosomal translocations is likely to shed more light on the molecular mechanisms responsible for the neoplastic transformation. The survey presents the main results obtained in these three areas and critically discusses them in the light of the current debate.
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PMID:Recent advances in lymphoma biology. 932 17

Anaplastic large-cell lymphoma (ALCL) is a recently proposed subset of non-Hodgkin's lymphoma. To determine whether Epstein-Barr virus (EBV) is associated with this lymphoma, we performed mRNA in situ hybridization on seven cases of ALCL using a probe consisting of an RNA sequence complementary to the transcripts of BamHIW fragment of the EBV genome. We detected BamHIW transcripts of EBV in the majority of atypical large cells of all cases of ALCL, but in none of three cases of lymphoblastic and small lymphocytic lymphomas. Furthermore, we detected latent membrane protein-1 (LMP1) in two cases of ALCL by means of immunofluorescence and immunoperoxidase stainings. These findings suggest that EBV is involved in the neoplastic transformation for ALCL as in the case of Hodgkin's disease, which shares several clinicopathologic features with ALCL.
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PMID:Detection of Epstein-Barr virus transcripts in anaplastic large-cell lymphomas by mRNA in situ hybridization. 941 87

Twenty-four hour MNNG-exposed Bloom syndrome (BS) B-lymphoblastoid cells with the potential to form single cell colonies in soft agar and nude mouse tumour (2/6 (33%) showed a simultaneous increase in the Ras-expressing cells (using monoclonal antibody to p21 transforming protein) from 20% (at 24 h) to 85% (on day 30). In contrast, there was an absence of Ras-positive cells in MNNG-exposed fresh lymphocytes (PBMCs) from a healthy subject and a presence of only 11-18% of Ras-positive cells in normal (GA3) and unexposed BS B-lymphoblastoid cells. The Western blot analysis using sera samples from Hodgkin's lymphoma patients showed the presence of proteins of 102 and 68 kDa which in 2D Westerns were observed to be unique to BS-MNNG cells with approximate pIs of 5.3 and 5.7, respectively. It is proposed that BS-MNNG cells provide an interesting in vitro human cell model to generate unique cancer-associated antigen(s) in addition to using this system to understand the primary events associated with neoplastic transformation.
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PMID:MNNG-transformed Bloom syndrome B-lymphoblastoids for the detection of Hodgkin's lymphoma-associated antigen in 2D Westerns. 956 42

There has been substantial advances in our understanding of the nature of the Hodgkin/Reed-Sternberg (H/RS) cell in recent years. There is now compelling evidence that the H/RS cells in the vast majority of cases of classical Hodgkin's disease (CHD) are derived from the B-cell lineage and a major clonal population is present. The immunoglobulin heavy chain variable region gene generally has a high load of somatic mutations suggesting that the H/RS cells are derived from germinal center (GC) (GC) or post-GC cells. The cellular milieu in the tumour is largely determined by the cytokines and chemokines secreted by the H/RS cells and the surrounding reactive elements. The pattern of secretion is partially determined by signals transduced through direct surface interactions between H/RS cells and infiltrating T-cells. Immunosuppressive cytokines and cytokines that preferentially induce a TH2 type of immune response may be partially responsible for the escape of the H/RS cells from immune surveillance. Multiple genes that have been shown to be involved in neoplastic transformation have been studied in HD. The significance of the data generated has been difficult to interpret. Efforts have been made to study the global gene expression pattern of the H/RS cells. There are many difficulties inherent in this approach, but new insight into the pathogenesis and evolution of HD would be expected from the studies.
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PMID:The Reed-Sternberg cell in classical Hodgkin's disease. 1127 42

In this review, we focus on new data from basic, translational and clinical research relating to the Epstein-Barr virus (EBV). Beside its well-known tropism for B lymphocytes and epithelial cells, EBV also infects T lymphocytes, monocytes and granulocytes. After primary infection, EBV persists throughout the life span in resting memory B cells, from where it is reactivated upon breakdown of cellular immunity. In the process of neoplastic transformation, the EBV-encoded latent membrane protein 1 (LMP1) oncogene represents the major driving force. LMP1 acts like a constitutively activated receptor of the tumor necrosis factor receptor family and allows the amplification or bypassing of physiological regulatory signals through direct and indirect interactions with proteins of the tumor necrosis factor receptor-associated factor (TRAF) family. TRAF2-mediated NF-kappaB activation, AP-1 induction and JAK3/STAT activation may result in sustained proliferation leading to lymphoma. The ability of LMP1 to suppress germinal center formation and its capacity to mediate its own transcriptional activation shed new light on the pathogenesis of EBV-associated latency type II lymphoproliferations like Hodgkin's disease and angioimmunoblastic lymphadenopathy. The carboxy terminus of LMP1 is also a reliable marker for individual EBV strain identification and thus offers new possibilities in tracing the molecular events leading to posttransplant lymphoproliferative disorders (PTLDs). Cytotoxic T lymphocytes directed against well-characterized epitopes of EBV latency genes represent an already successful and promising therapeutic approach to EBV-associated lymphomas, in particular PTLDs.
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PMID:The role of Epstein-Barr virus in neoplastic transformation. 1140 95

The mRNA expression profile of a tumor reflects the unique genetic alterations present and is predictive of the clinical and biological characteristics of the tumor. Novel techniques have been developed to determine the global gene expression pattern of normal and neoplastic tissues. A cDNA microarray uniquely suitable for the analysis of B-cell non-Hodgkin's lymphomas (B-NHL) has been developed and preliminary analysis on diffuse large B-cell lymphoma (DLBCL), follicular lymphoma (FL) and B-chronic lymphocytic leukemia (CLL) has been performed. These studies indicate that: 1) it is feasible to determine the gene expression profiles of archival lymphoma samples frozen and stored in a clinical setting, 2) the expression profile of these 3 types of lymphoproliferative disorders are distinctive, 3) DLBCL can be divided into at least 2 major subgroups according to their pattern of expression of B-cell associated genes and 4) the gene expression patterns in DLBCL appear to have prognostic significance. A larger study of DLBCL is currently underway to confirm and extend our findings. Gene expression profiles will be correlated with cytogenetic and clinical data to identify distinctive profiles that are of clinical and biological significance and to delineate key genetic lesions that determine these profiles. The new information will allow the design of a simpler and less expensive array for clinical use. The diagnostic array could provide rapid molecular characterization of every B-NHL at presentation for optimal treatment decisions and prognostication. It is anticipated that this project will advance our understanding of the molecular mechanisms in the neoplastic transformation of B-lymphoid cells and the new insights will help to identify promising molecular targets for therapeutic intervention.
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PMID:Gene expression analysis in aggressive NHL. 1175 4


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