UMLS:C0019829 - FACTA Search

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

A new monoclonal antibody (MUM1p) was used to study the cell/tissue expression of human MUM1/IRF4 protein, the product of the homologous gene involved in the myeloma-associated t(6;14) (p25;q32). MUM1 was expressed in the nuclei and cytoplasm of plasma cells and a small percentage of germinal center (GC) B cells mainly located in the "light zone." Its morphologic spectrum ranged from that of centrocyte to that of a plasmablast/plasma cell, and it displayed a phenotype (MUM1(+)/Bcl-6(-)/Ki67(-)) different from that of most GC B cells (MUM1(-)/Bcl-6(+)/Ki67(+)) and mantle B cells (MUM1(-)/Bcl-6(-)/Ki67(-)). Polymerase chain reaction (PCR) analysis of single MUM1(+ )cells isolated from GCs showed that they contained rearranged Ig heavy chain genes with a varying number of V(H) somatic mutations. These findings suggest that these cells may represent surviving centrocytes and their progeny committed to exit GC and to differentiate into plasma cells. MUM1 was strongly expressed in lymphoplasmacytoid lymphoma, multiple myeloma, and approximately 75% of diffuse large B-cell lymphomas (DLCL-B). Unlike normal GC B cells, in which the expression of MUM1 and Bcl-6 were mutually exclusive, tumor cells in approximately 50% of MUM1(+) DLCL-B coexpressed MUM1 and Bcl-6, suggesting that expression of these proteins may be deregulated. In keeping with their proposed origin from GC B cells, Hodgkin and Reed-Sternberg cells of Hodgkin's disease consistently expressed MUM1. MUM1 was detected in normal and neoplastic activated T cells, and its expression usually paralleled that of CD30. These results suggest that MUM1 is involved in the late stages of B-cell differentiation and in T-cell activation and is deregulated in DLCL-B. (Blood. 2000;95:2084-2092)
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PMID:A monoclonal antibody (MUM1p) detects expression of the MUM1/IRF4 protein in a subset of germinal center B cells, plasma cells, and activated T cells. 1070 78

MUM1/IRF4 is a myeloma-associated oncogene transcriptionally activated as a result of t(6;14)(p25,q32) chromosomal translocation and by virtue of its juxtaposition to the immunoglobulin heavy chain gene (IgH) locus. When this oncogene becomes non-functional, no activated B/T lymphocytes and Ig secreting plasma cells are observed, suggesting that MUM1/IRF4 is crucial for lymphoid development. Its expression was analyzed in both reactive lymphoid and lymphoma tissues by means of an immunohistochemical technique using specific goat antiserum against MUM1/IRF4. This analysis detected a 50 kDa MUM1 product whose localization was restricted to the nuclei of the lymphocytes. The MUM1+ cells in reactive lymph nodes were found to consist of plasma cells and a small fraction (approximately 7.9%) of B cells harboring CD20+CD38+, which were located in the light zone of the germinal center. MUM1 expression in peripheral blood B/T lymphocytes was upregulated by mitogenic stimuli, suggesting that MUM1 positivity represents the activated state of the B/T cells. In B cell non-Hodgkin's lymphoma (NHL), MUM1 expression was observed in 73.2% (30/41) of diffuse large B cell lymphoma (DLBCL), 20% (1/5) of marginal zone lymphoma (MZL) and 43% (3/7) of small lymphocytic lymphoma (SLL) cases, whereas it was not seen in any cases of mantle cell lymphoma (MCL) or follicle center lymphoma (FCL). Also, MUM1 was stained at high intensity in various types of T cell lymphomas including adult T cell leukemia/lymphoma (ATL/L) and anaplastic large cell lymphoma (ALCL) and in the majority of Hodgkin's diseases. Our results suggest that a major proportion of lymphomas comprise either physiologically or aberrantly activated neoplastic lymphocytes expressing the MUM1 protein.
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PMID:MUM1/IRF4 expression as a frequent event in mature lymphoid malignancies. 1072 Jan 41

This study was aimed at defining the histogenesis of the pathologic spectrum of lymphoma arising in the context of human immunodeficiency virus (HIV) infection. Toward this aim, 87 AIDS-related non-Hodgkin lymphomas (AIDS-NHL) and 16 Hodgkin lymphomas arising in HIV+ patients (HIV-HL) were comparatively analyzed for the expression pattern of several B-cell histogenetic markers, including BCL-6 (expressed by centroblasts and centrocytes), MUM1/IRF4 (expressed by late centrocytes and post-germinal center [GC] B cells), and CD138/syn-1 (expressed by post-GC B cells). Expression of MUM1, BCL-6, and syn-1 segregated 3 major phenotypic patterns among AIDS-NHL and HIV-HL: (1) the BCL-6+/MUM1-/syn-1- pattern, selectively clustering with a large fraction of AIDS-Burkitt lymphoma (17 of 19) and of systemic AIDS-diffuse large cell lymphoma (12 of 16); (2) the BCL-6-/MUM1+/syn-1- pattern, associated with a fraction of AIDS-immunoblastic lymphoma (8 of 24); and (3) the BCL-6-/MUM1+/syn-1+ pattern, associated with systemic and primary central nervous system immunoblastic lymphoma (14 of 24) and with primary effusion lymphoma (10 of 10), plasmablastic lymphoma of the oral cavity (7 of 7), and HIV-HL (15 of 16). Analysis of nonneoplastic lymph nodes showed that the 3 phenotypic patterns detected in AIDS-NHL and HIV-HL correspond to distinct stages of physiologic B-cell development-centroblasts (BCL-6+/MUM1-/syn-1-), late GC/early post-GC B cells (BCL-6-/MUM1+/syn-1-), and post-GC B cells (BCL-6-/MUM1+/syn-1+). Expression of the Epstein-Barr virus-encoded latent membrane protein-1 clustered with the BCL-6-/MUM1+/syn-1+ profile throughout the clinicopathologic spectrum of AIDS-NHL and HIV-HL. Overall, these results define novel histogenetic subsets of AIDS-NHL and HIV-HL and may provide novel tools for refining the diagnosis of these disorders.
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PMID:Expression profile of MUM1/IRF4, BCL-6, and CD138/syndecan-1 defines novel histogenetic subsets of human immunodeficiency virus-related lymphomas. 1115 93

Biological and clinical studies have shown that Hodgkin's disease (HD) can be divided into two major categories, termed nodular lymphocyte predominance HD (NLP HD) and classic HD (CHD). Within CHD four subtypes have been distinguished: nodular sclerosis, mixed cellularity, lymphocyte rich and lymphocyte depletion. To refine the histogenesis of the pathological spectrum of HD, 75 CHD and 13 NLP HD were analysed for the expression pattern of MUM1/IRF4 (Multiple Myeloma-1/Interferon Regulatory Factor-4), a lymphocyte-specific member of the IRF family, that is expressed by late centrocytes and post-germinal centre (GC) B cells. MUM1 reacted with Hodgkin's and Reed-Sternberg (HRS) cells of all CHD cases (75/75 cases), with a moderate to strong staining intensity. Conversely, lymphocyte and histiocyte (L & H) cells, the putative tumour cells of NLP HD, were negative for MUM-1 expression (9/13 cases) or displayed a weak reactivity for the antigen in < 10% neoplastic cells (4/13 cases). With respect to HD microenvironment, NLP HD displayed numerous MUM1-positive T lymphocytes located in close proximity to L & H cells whereas, in CHD, MUM1-positive T lymphocytes appeared to be distributed randomly with no specific relationship with HRS cells. Overall, this study shows that MUM1 expression differs in L & H cells versus HRS cells, corroborating the notion that NLP HD and CHD represent different stages of B-cell differentiation. As MUM1-positive T lymphocytes form rosettes around tumour cells of NLP HD, but not of CHD, these data point also to differences in the microenvironment of NLP HD and CHD, and postulate an interactive role of MUM1-positive T lymphocytes with L & H cells.
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PMID:Expression pattern of MUM1/IRF4 in the spectrum of pathology of Hodgkin's disease. 1197 19

The World Health Organization (WHO) classification of Hodgkin lymphoma (HL) distinguishes two types: Classical Hodgkin lymphoma (CHL) and nodular lymphocyte predominant Hodgkin lymphoma (NLPHL). Both groups have in common that they mostly derive from B cells with rare classical cases originating from T cells. They differ in their histomorphology, immunophenotype, and clinical behavior. One of the subtypes of CHL, designated as lymphocyte-rich classical Hodgkin lymphoma (LRCHL), shares some morphological features with NLPHL. The transcription factors BSAP, BOB.1, Oct2 and MUM1 are sequentially expressed in normal B-cell development. In order to investigate the relationship between the CHL subgroups and NLPHL, we examined the protein expression of these transcription factors using immunohistochemistry in 15 reactive processes and 4 different subtypes of 58 HL cases. Our findings underline the B-cell origin of HL, without evidence, that reactive processes like progressively transformed germinal centers (PTGCs) are precursor lesions of HL. Furthermore, they demonstrate that LRCHL is distinct from NLPHL and that it is closely related to the mixed cellularity CHL (MCHL) in respect of BSAP, BOB.1, and Oct2 expression. It therefore occupies an intermediate position between MCHL and NLPHL. Based on MUM1 staining, LRCHL exhibits a more mature phenotype than NLPHL.
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PMID:Expression patterns of transcription factors in progressively transformed germinal centers and Hodgkin lymphoma. 1264 20

Controversy still exists over the response to therapy and prognosis of patients with primary mediastinal B-cell lymphoma (PMBL). Recent data from the International Extranodal Lymphoma Study Group (IELSG) suggest that a MACOP-B (methotrexate, adriamycin, cyclophosphamide, vincristine, prednisone, bleomycin) chemotherapy regimen followed by radiotherapy may be a better induction strategy than other previously used treatments. Although the pathobiology of PMBL has been widely studied, its precise histology, phenotype, and molecular characteristics are still not clear. To date, phenotypic analysis has revealed the following phenotype: positivity for CD45 and CD20, but negativity for CD3, CD10, CD21, Class I/II major histocompatibility antigens, and a variety of other immunohistochemical markers. CD79a is generally detected, despite an absence of surface immunoglobulins (Igs). CD30 staining is observed in most cases, but is weaker and less homogeneous than in classic Hodgkin's lymphoma or anaplastic large cell lymphoma. BCL-2 protein is usually expressed but there are few data describing the expression of MUM1/IRF4, PAX5/BSAP, BCL-6, or the B-cell transcription factors BOB.1, Oct-2, and PU.1. Cytogenetic studies reveal gains in segments of chromosome 9p, including amplification of the REL proto-oncogene and the tyrosine kinase gene JAK2. Other molecular findings include: C-myc mutations or rearrangements, p53 mutations, IgV(H), gene mutations, and bcl-2 and mal over-expression. bcl-6 mutations and bcl-2 gene rearrangements are generally absent, suggesting that PMBL is of pre-germinal center (GC) origin. However, two recent reports show isotype-switched Ig genes with a high frequency of somatic hypermutations as well as variants in the 5' noncoding region of the bcl-6 gene. The IELSG collected 137 PMBL cases for extensive pathologic review. Histologically, the lymphomatous growth was predominantly diffuse with sclerosis that induced compartmentalized cell aggregation. It consisted of large cells with varying degrees of nuclear polymorphism and clear to basophilic cytoplasm. Molecular analysis was performed on 40 cases and showed novel findings. More than half of the cases displayed bcl-6 gene mutations, which usually occurred together with functioning somatic IgV(H) gene mutations, and BCL-6 and/or MUM1/IRF4 expression. The present study supports the concept that PBML is derived from activated GC or post-germinal center cells. However, it differs from other aggressive B-cell lymphomas in that it shows defective Ig production despite the expression of Oct-2, BOB.1, and PU.1 transcription factors, and a lack of IgV(H) gene crippling mutations.
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PMID:Pathobiology of primary mediastinal B-cell lymphoma. 1520 21

We identified the human germinal center-associated lymphoma (HGAL) in gene-expression profiling studies of diffuse large B-cell lymphoma (DLBCL). The expression of HGAL correlated with survival in patients with DLBCL. The HGAL gene is the human homolog of M17, a mouse gene expressed specifically in normal germinal center (GC) B cells. We generated a monoclonal antibody against the HGAL protein and show that HGAL is expressed in the cytoplasm of GC lymphocytes and in lymphomas of GC derivation. Among 727 lymphomas tested by immunohistochemistry on tissue microarrays, HGAL staining was found in follicular lymphomas (103 of 107), Burkitt lymphomas (40 of 40), mediastinal large B lymphomas (7 of 8), and in DLBCLs (103 of 151). Most marginal zone lymphomas lacked HGAL staining. Lymphocyte-predominant Hodgkin lymphomas (12 of 17) and, surprisingly, classical Hodgkin lymphomas (78 of 107) were found to be positive. Hierarchical clustering of comparative immunohistologic results in DLBCLs demonstrates that the expression of HGAL is similar to 2 other GC-associated proteins, BCL6 and CD10, but different from 2 markers associated with a non-GC phenotype, MUM1/IRF4 and BCL2. The restricted expression and GC specificity of HGAL protein suggest that it may have an important role in the diagnosis of specific lymphomas, and, potentially in the identification of subtypes associated with different prognoses.
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PMID:Expression of the human germinal center-associated lymphoma (HGAL) protein, a new marker of germinal center B-cell derivation. 1567 69

Diffuse large B-cell lymphomas (DLBCL) represent the most common type of adult non-Hodgkin's lymphomas in Western countries and are characterized by heterogeneous clinical, histological, immunophenotypic and genetic features. Recent investigations using cDNA and oligonucleotide microarrays have identified molecularly distinct groups of DLBCL with respect to the B-cell differentiation gene expression profile: the germinal center (GC) B-cell-like DLBCL, the activated B-cell-like DLBCL and the type 3 DLBCL. The GC B-cell-like DLBCL were characterized by the expression of genes of the normal GC B-cells, the activated B-cell-like DLBCL were characterized by the expression of genes that are normally induced luring in vitro activation of peripheral blood B-cells, while the type 3 DLBCL did not express either set of genes at a high level. Patients with GC B-cell-like DLBCL had more favorable clinical outcome than those with activated B-cell-like or type 3 DLBCL. Immunohistochemical studies have shown that the bc16/CD10/MUM1/CD138 B-cell differentiation immunophenotypes are prognostically relevant and may predict the cDNA classification in a sizable fraction of DLBCL. In the last few years, there has been accumulating molecular and immunohistochemical evidence indicating links between B-cell differentiation gene expression profiles and expression of apoptosis and cell cycle-associated genes in DLBCL. The present review summarizes data with respect to the relationships between B-cell differentiation, apoptosis and proliferation in DLBCL.
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PMID:B-cell differentiation, apoptosis and proliferation in diffuse large B-cell lymphomas. 1581 58

Although diffuse large B-cell lymphoma (DLBCL) is the most common type of non-Hodgkin lymphoma, it is both clinically and morphologically heterogenous. The present study investigates the significance of survivin and a novel monoclonal antibody (MAb), T332, immunohistochemically for predicting the prognoses of DLBCL and its subtypes classified as germinal center B-cell-like type (GCB) and non-GCB type (NGCB) based on the expression profiles of CD10, bcl-6, and MUM1. A total of 60 cases of DLBCL (GCB, n = 22; NGCB, n = 38) were examined for the expression of survivin and T332 antigen. Survivin(+) DLBCL had a significantly worse prognosis (P = 0.01) than survivin(-) cases, as already reported, while survivin(+) GCB or NGCB tended to have poor prognoses (P = 0.06 and 0.07, respectively). However, T332(+) DLBCL and NGCB had significantly more unfavorable prognoses than T332(-) cases (P = 0.01 and 0.02, respectively) while there was no significant survival difference between the T332(+) and T332(-) groups of GCB (P = 0.11). Interestingly DLBCL coexpressing survivin and T332 (n = 13) had a significantly worse prognosis (P = 0.009) than the remaining single positive and double negative cases (n = 31). In conclusion, survivin and the novel MAb, T332, might be a good predictor of DLBCL and its subtypes.
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PMID:Expression of survivin and of antigen detected by a novel monoclonal antibody, T332, is associated with outcome of diffuse large B-cell lymphoma and its subtypes. 1594 89

The bcl6/CD10/MUM1/CD138 B-cell differentiation immunophenotypes were analysed in 101 cases of classical Hodgkin lymphomas (cHL) aiming to elucidate their histogenesis. Three major bcl6/CD10/MUM1/CD138 immunophenotypes were distinguished on the basis of the immunohistochemical positivity of Hodgkin and Reed-Sternberg (H/RS) cells: (a) the late germinal center (GC)/early post-GC B-cell-like immunophenotype (bcl6-/CD10-/MUM1+/CD138-); 59/101 cases (59%), (b) the post-GC B-cell-like immunophenotype (bcl6-/CD10-/MUM1+/CD138+); 24/101 cases (24%) and (c) the indeterminate immunophenotype (bcl6+/CD10-/MUM1+/CD138-: 14 cases and bcl6+/CD10-/MUM1+/CD138+: four cases); 18/101 cases (18%). The above findings indicate that H/RS cells in most cHL display bcl6/CD10/MUM1/CD138 immunophenotypes consistent with late GC/early post-GC or post-GC B-cell differentiation. In addition, H/RS cells in a small fraction of cHL display indeterminate bcl6/CD10/MUM1/CD138 immunophenotypic profiles which are characterized by simultaneous expression of GC, late GC/early post-GC and post-GC B-cell differentiation proteins. These immunophenotypic profiles do not correspond to the differentiation immunophenotypes of normal B-cells and their identification in a part of cHL suggests that the differentiation process of H/RS cells is not complete in a fraction of these cells and/or is still ongoing at the time of observation.
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PMID:B-cell differentiation immunophenotypes in classical Hodgkin lymphomas. 1639 74

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