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 utility of polymerase-mediated assays in the detection of the t(11;14) involving the bcl-1 major translocation cluster (bcl-1 MTC) was evaluated by analyzing DNA from 33 patients with mantle cell lymphoma, 14 patients with other non-Hodgkin's lymphomas, and five patients with reactive lymphoid hyperplasia. The polymerase chain reaction (PCR) assay was performed using a consensus immunoglobin heavy-chain joining region primer in conjunction with a chromosome 11 specific oligonucleotide primer flanking the translocation site. The sensitivity and specificity of the assay were confirmed by correlation of the (PCR) assay data with restriction analysis. Rearrangements at the bcl-1 MTC were detected in 13 (39%) of 33 cases of mantle cell lymphoma by PCR and in 13 (48%) of 27 cases by restriction analysis. Amplicons were detectable by PCR in 85% (11 of 13) of the cases shown to be bcl-1 rearranged by restriction analysis. Failure to detect amplification products in DNA samples from non-mantle cell lymphomas and reactive follicular hyperplasia further confirmed the specificity of the assay. Sequential hybridization of the PCR products with oligonucleotide probes 3' to the bcl-1 MTC primer revealed that the breakpoints in the bcl-1 MTC were clustered around an Sst I restriction site over a range of 170 base pairs. The study demonstrates that PCR-mediated assay for the detection of the t(11;14) at the bcl-1 MTC is specific and sensitive and can be used as an adjunct to restriction analysis in routine diagnostics.
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PMID:Polymerase chain reaction detection of the t(11;14) translocation involving the bcl-1 major translocation cluster in mantle cell lymphoma. 773 55

Clonal rearrangements of the bcl-1 and bcl-2 protooncogenes are found in many B-lineage non-Hodgkin's lymphomas (NHL) and may play a role in their pathogenesis. We investigated rearrangements of the bcl-1 and bcl-2 protooncogenes in 13 cases of B lineage diffuse small cleaved-cell lymphoma (DSCL), and correlated the results with clinical history, immunophenotype, and outcome. Six cases showed bcl-2 rearrangements, including four patients with an antecedent follicular small cleaved-cell lymphoma (FSCL). Two patients had a bcl-1 rearrangement, including one with a previous FSCL. Of the five patients who lacked detectable bcl-1 or bcl-2 rearrangements, one had an FSCL history. Similar to the lack of correlation between clinical history and genotype, there was no correlation between genotype and immunophenotype. Our results indicate that although DSCL is a morphologically uniform disease, different molecular genetic pathways are involved in its genesis. Follow-up showed four of the six DSCL patients with bcl-2 rearrangements were alive with a median survival of 56 months, whereas the median survival of the seven patients lacking a bcl-2 rearrangement was 17 months and included only one survivor. Thus bcl-2 rearrangements in DSCL may define a patient subset with a more indolent genetic abnormality and prolonged survival.
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PMID:The presence of bcl-1 and bcl-2 gene rearrangements in diffuse small cleaved-cell lymphoma. A disease with diverse molecular and immunophenotypic findings. 798 93

Histological subtyping of non-Hodgkin's lymphomas is of prognostic significance. Current classification systems subdivide them into low-, intermediate-, and high-grade malignancies. These subgroups are largely supported by clinical findings, but immunophenotyping and genotyping have shown that several of these histologically defined subcategories are heterogeneous. This is exemplified by the 'diffuse small cleaved-cell lymphoma' which comprises B-cell and T-cell lymphomas. Moreover, within the B-cell lymphomas, several entities have been included, which recapitulate the different compartments present in the reactive B follicle, e.g., the follicle centre, the mantle, and the marginal zone. Mantle-cell lymphomas have been identified in the United States as mantle-zone lymphomas and as intermediate differentiated lymphomas and in Europe as centrocytic lymphomas. Morphology, immunophenotyping, and cytogenetics of these three lymphomas support their similarity and underline their distinction from follicle centre-cell lymphomas as well as from small lymphocytic lymphomas. All three are composed of a mixture of small round and small cleaved cells, expressing several B-cell markers, surface immunoglobulins, and CD5, but lacking CD10 expression. They often carry the translocation t(11;14) with rearrangement of bcl-1/PRAD1 gene. The behaviour and responsiveness to therapy of mantle-cell lymphomas has not been fully documented yet. In order to obtain these data, precise subtyping of non-Hodgkin's lymphomas--not only based on morphology, but supported by immunophenotyping and cytogenetic analysis--is now mandatory.
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PMID:Mantle-cell lymphoma. 817 14

The wide clinicopathologic heterogeneity of non-Hodgkin's lymphoma is reflected by the various molecular pathways underlying non-Hodgkin's lymphoma pathogenesis, including activation of dominantly acting oncogenes, deletion and inactivation of tumor-suppressor genes, viral infection, deregulation of cytokine networks, and chronic antigenic stimulation. Molecular lesions involving protooncogenes include activation of bcl-2 and bcl-1 in specific subsets of low-grade non-Hodgkin's lymphomas and c-myc in a proportion of intermediate- and high-grade non-Hodgkin's lymphomas. The deregulation of these genes promotes cell growth or protects the tumor population from programmed cell death, or both. Additional genetic abnormalities representing putative sites of novel oncogenes contributing to lymphomagenesis include chromosomal breaks at 3q27 in intermediate-grade non-Hodgkin's lymphoma and at 9p13 in small lymphocytic lymphoma. The role of inactivation of tumor-suppressor loci is best exemplified by the frequent inactivation of p53 in Burkitt's lymphoma and by the recurrent deletion of 6q25-q27 and 6q21-q23 in intermediate- and high-grade non-Hodgkin's lymphoma, respectively. Infection by Epstein-Barr virus occurs in a variable fraction of high-grade non-Hodgkin's lymphomas, whereas it is usually absent in other types of non-Hodgkin's lymphoma. Other mechanisms supporting non-Hodgkin's lymphoma growth and development include autocrine or paracrine cytokine loops, or both, and clonal expansion through antigen receptor stimulation. The heterogeneity of non-Hodgkin's lymphoma pathogenesis provides a framework for the development of novel classification methods of potential clinical relevance.
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PMID:Biologic and molecular characterization of non-Hodgkin's lymphoma. 821 89

Primary central nervous system lymphomas (PCNSL) show increased incidence both in immunocompromised high-risk groups and in the general population. They are extranodal diffuse non-Hodgkin's lymphomas with a morphology similar to systemic lymphomas, but differ in their biological and molecular behaviour. The majority are large B-cell variants of high-grade malignancy; low-grade subtypes and T-cell lymphomas are rare; up to 50% remain unclassified according to the New Working Formulation and updated Kiel classification. Monoclonality of immunoglobulin receptor gene rearrangement can be diagnostically useful. The pathogenesis of PCNSL is obscure. Epstein-Barr virus (EBV) genome/proteins expression in two-thirds of HIV-related PCNSL but only in 15% of those in immunocompetent patients suggest different EBV latency stages in both types; human herpesvirus type 6 does not appear to play a pathogenic role. Comparison of expression patterns of integrin chains and adhesion molecules are very similar for PCNSL and nodal lymphomas suggesting that they are not selective mediators of lymphoma cell homing to the brain. In HIV-negative PCNSL they appear not to be influenced by EBV. Studies of protooncogenes (bcl-1 and bcl-2 genes) revealed no rearrangement in PCNSL, suggesting that they are not involved in the pathogenesis of PCNSL that probably do not differ cytogenetically from nodal B-cell lymphomas. Since most of the currently known molecular parameters are probably not the primary pathogenic events, the molecular genetics and pathogenesis of PCNSL are still to be elucidated.
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PMID:Primary central nervous system lymphomas--new pathological developments. 852 72

Mantle cell lymphomas (MCLs) are molecularly characterized by bcl-1 rearrangement and constant cyclin D1 (PRAD-1/CCND1) gene overexpression. Cyclin D1 is a G1 cyclin that participates in the control of the cell cycle progression by interacting with the retinoblastoma gene product (pRb). Inactivation of the Rb tumor suppressor gene has been implicated in the development of different types of human tumors including some high grade non-Hodgkin's lymphomas. To determine the role of the retinoblastoma gene in the pathogenesis of MCLs and its possible interaction with cyclin D1, pRb expression was examined in 23 MCLs including 17 typical and 6 blastic variants by immunohistochemistry and Western blot. Rb gene structure was studied in 13 cases by Southern blot. Cytogenetic analysis was performed in 5 cases. The results were compared with the cyclin D1 mRNA levels examined by Northern analysis, and the proliferative activity of the tumors was measured by Ki-67 growth fraction and flow cytometry. pRb was expressed in all MCLs. The expression varied from case to case (mean, 14.1% of positive cells; range, 1.3 to 42%) with a significant correlation with the proliferative activity of the tumors (mitotic index r = 0.85; Ki-67 r = 0.7; S phase = 0.73). Blastic variants showed higher numbers of pRb-positive cells (mean, 29%) than the typical cases (10%; P < 0.005) by immunohistochemistry and, concordantly, higher levels of expression by Western blot. In addition, the blastic cases also had an increased expression of the phosphorylated protein. No alterations in Rb gene structure were observed by Southern blot analysis. Cyclin D1 mRNA levels were independent of pRb expression and the proliferative activity of the tumors. These findings suggest that pRb in MCLs is normally regulated in relation to the proliferative activity of the tumors. Cyclin D1 overexpression may play a role in the maintenance of cell proliferation by overcoming the suppressive growth control of pRb.
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PMID:Expression of retinoblastoma gene product (pRb) in mantle cell lymphomas. Correlation with cyclin D1 (PRAD1/CCND1) mRNA levels and proliferative activity. 862 27

Mantle cell lymphoma (formerly known as intermediate lymphocytic lymphoma, diffuse centrocytic lymphoma, or diffuse small cleaved lymphoma) is one of the small cell non-Hodgkin lymphoma entities that is clinically more aggressive than small lymphocytic lymphoma, and needs to be separated from it. Mantle cell lymphoma is strongly associated with the t(11;14) chromosomal translocation that rearranges the bcl-1 oncogene (PRAD-1 gene) and immunoglobulin heavy chain gene. In this study, we developed a nested polymerase chain reaction system to evaluate the t(11;14) translocation. The study material consisted of 10 mantle cell lymphomas fulfilling the criteria suggested by other authors (P. M. Banks et al. Surg Pathol 16:637, 1992). A novel nested polymerase chain reaction system was used to evaluate the bcl-1 breaks in the major translocation cluster using two successive polymerase chain reaction amplifications. This reaction yielded a background-free single product of the size of 200 to 300 base pairs in four of 10 mantle cell lymphomas. The identity of the product from the nested polymerase chain reaction was confirmed by Southern blotting followed by hybridization with a specific probe. The amplification products were also evaluated by Sst-I, Alu-I, Dde-I, and Ita-I restriction enzymes and showed different patterns of digestion reflecting individual differences between the MTC/ IgH junctions. A selection of other low-grade lymphomas, including lymphocytic, follicular, and mucosa-associated lymphoid tissue lymphoma, and hairy cell leukemia and 29 hyperplastic lymph nodes were negative. This nested polymerase chain reaction system for the t(11;14) translocation involving major translocation cluster offers a convenient specific identification for mantle cell lymphoma. However, this test has a limited diagnostic power because only about half of the mantle cell lymphomas show the bcl-1 breaks in the major translocation cluster. The test performs well in formaldehyde-fixed and paraffin-embedded material, allowing the study of large numbers of retrospective cases of mantle cell lymphomas.
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PMID:Molecular diagnosis of mantle cell lymphoma in paraffin-embedded tissue. 872 72

We conducted an ultrastructural study in 22 cases of B-lymphoproliferative disorders in leukaemic phase bearing the t(11;14) translocation. The features of peripheral blood leukaemic cells in nine cases of mantle cell lymphoma (MCL) were compared to those diagnosed as B-prolymphocytic leukaemia (B-PLL) (five cases), splenic lymphoma with villous lymphocytes (SLVL) (four cases), lymphoplasmocytic lymphoma (LPL) (one case), chronic lymphocytic leukaemia with > 10% prolymphocytes (CLL/ PL) (one case) and unclassified B-non Hodgkin's lymphoma (B-NHL) (two cases). The ultrastructural characteristics were also compared to those present in B-NHL without t(11;14), including cases of follicular centre lymphoma (FCL). This study shows that MCL has distinct ultrastructural features including a cleaved or indented nucleus with an even heterochromatin distribution, an absent or inconspicuous nucleolus, low N/C ratio, abundant mitochondria, a well developed Golgi zone, profiles of endoplasmic reticulum and centrioles. This pattern clearly differs from that found in FCL cells. The nuclear pattern of MCL cells also differed from the cells in the other disorders with t(11;14), but shared an organelle-rich cytoplasm, and features which were not apparent in cases without t(11;14). The cytoplasmic changes observed in cells bearing t(11;14) suggest increased cellular activity which may relate to the chromosome translocation and the resulting over-expression of bcl-1.
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PMID:The ultrastructure of mantle cell lymphoma and other B-cell disorders with translocation t(11;14)(q13;q32). 875 96

Clonality of T- and B-cell lymphoproliferative disorders can be determined by gene rearrangement studies when morphology and surface immunostaining are nondiagnostic. TcR and lg gene rearrangements have been demonstrated in many different hematologic disorders and TcR gene rearrangement has been particularly useful in the diagnosis of patients with CD8 large granular lymphocyte leukemias. TcR gene rearrangement may also be useful to distinguish Hodgkin's disease from T-cell non-Hodgkin's lymphoma. Gene rearrangement is usually performed by Southern analysis, and it is beneficial to run multiple enzyme-probe combinations to maximize the detection of clonal rearrangements. More recently, several laboratories have begun to use polymerase chain reaction (PCR) for gene rearrangement analysis. PCR offers an improved turnaround time, eliminates partial digestion artifacts, and allows for the use of paraffin embedded material. In addition to rearrangements of the TcR and lg genes, analysis of alterations in other genes such as bcl-1, bcl-2, bcl-6, and c-myc are also useful as clonal markers and aid in the classification of lymphomas.
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PMID:Molecular genetics and lymphoproliferative disorders. 895 2

Sixty-four cases of mantle cell (centrocytic) non-Hodgkin's lymphomas have been analyzed for their cytomorphologic features, proliferation indices, bcl-1 rearrangements, p53 expression patterns, and DNA content by both interphase cytogenetic and DNA flow cytometric analyses. According to cytomorphology, three subtypes were recognized: a common, a lymphoblastoid, and a pleomorphic variant of mantle cell lymphoma (MCL). Blastoid MCL subtypes were characterized by distinctly elevated mitotic counts (57 and 51/10 HPF v 21/10 high-power fields in common MCL), proliferation indices (58% and 53% v 27% in common types, respectively; P < .001), frequent bcl-1 rearrangements at the major translocation cluster locus (59% v 40%), and overexpression of p53 (21% v 6%). However, the most interesting finding was a striking tendency of blastoid MCL subtypes to harbor chromosome numbers in the tetraploid range (36% of lymphoblastoid and 80% of pleomorphic types v 8% of common variants, P < .001), a feature clearly separating these neoplasms from other types of B-cell non-Hodgkin's lymphoma and possibly being related to cyclin D1 overexpression. Our data indicate that, although characterized by a uniform immunophenotype and common biologic background, MCL shows a broad spectrum of morphologic features ranging from small cell to blastoid types and that the morphologic spectrum is mirrored by distinct biologic features.
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PMID:Blastoid variants of mantle cell lymphoma: frequent bcl-1 rearrangements at the major translocation cluster region and tetraploid chromosome clones. 902 66


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