Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.4.24.11 (CD10)
 9,792 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

B lymphocyte-induced maturation protein-1 (Blimp-1) is a transcriptional repressor that is sufficient to trigger terminal differentiation in the B cell lymphoma BCL-1. In this study, we have determined the expression pattern of Blimp-1 in vivo in primary and secondary lymphoid organs of humans and immunized mice. Blimp-1 is expressed in plasma cells derived from either a T-independent or T-dependent response in plasma cells that have undergone isotype switching and those resulting from secondary immunization. Blimp-1 is also present in long-lived plasma cells residing in the bone marrow. However, Blimp-1 was not detected in memory B cells. This expression pattern provides further evidence of a critical role for Blimp-1 in plasma cell development, supporting earlier studies in cultured lines. Significantly, Blimp-1 was also found in a fraction (4-15%) of germinal center B cells in murine spleen and human tonsils. Blimp-1 expression in the germinal center is associated with an interesting subset of cells with a phenotype intermediate between germinal center B cells and plasma cells. In the mouse, Blimp-1(+) germinal center B cells peak at day 12 postimmunization and disappear soon thereafter. They are not apoptotic, some are proliferating, they express germinal center markers peanut agglutinin or CD10 but not Bcl-6, and most express CD138 (syndecan-1), IRF4, and cytoplasmic Ig. Together, these data support a model in which B cell fate decisions occur within the germinal center and Blimp-1 expression is critical for commitment to a plasma cell, rather than a memory cell, fate.
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PMID:Commitment of B lymphocytes to a plasma cell fate is associated with Blimp-1 expression in vivo. 1106 98

Although primary mediastinal (thymic) large B-cell lymphoma has been primarily studied, its precise phenotype, molecular characteristics, and histogenesis are still a matter of debate. The International Extranodal Lymphoma Study Group collected 137 such cases for extensive pathological review. Histologically, the lymphomatous growth was predominantly diffuse with fibrosis that induced compartmentalized cell aggregation. It consisted of large cells with varying degrees of nuclear polymorphism and clear to basophilic cytoplasm. On immunohistochemistry, the following phenotype was observed: CD45(+), CD20(+), CD79a(+), PAX5/BSAP(+), BOB.1(+), Oct-2(+), PU.1(+), Bcl-2(+), CD30(+), HLA-DR(+), MAL protein(+/-), Bcl-6(+/-), MUM1/IRF4(+/-), CD10(-/+), CD21(-), CD15(-), CD138(-), CD68(-), and CD3(-). Immunoglobulins were negative both at immunohistochemistry and in situ hybridization. Molecular analysis, performed in 45 cases, showed novel findings. More than half of the cases displayed BCL-6 gene mutations, which usually occurred along with functioning somatic IgV(H) gene mutations and Bcl-6 and/or MUM1/IRF4 expression. The present study supports the concept that a sizable fraction of cases of this lymphoma are from activated germinal center or postgerminal center cells. However, it differs from other aggressive B-cell lymphomas in that it shows defective immunoglobulin production despite the expression of OCT-2, BOB.1, and PU.1 transcription factors and the lack of IgV(H) gene crippling mutations.
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PMID:Primary mediastinal B-cell lymphoma: high frequency of BCL-6 mutations and consistent expression of the transcription factors OCT-2, BOB.1, and PU.1 in the absence of immunoglobulins. 1250 7

Recent studies with cDNA microarrays showed that diffuse large B-cell lymphoma (DLBCL) cases with gene expression profiles similar to germinal center (GC) B cells had much better prognosis than DLBCL cases with gene expression profiles resembling activated B cells. The goal of the current study is to evaluate if using a panel of GC B-cell (CD10 and Bcl-6) and activation (MUM1/IRF4 and CD138) markers by immunohistochemistry defines prognosis in patients with de novo DLBCL. Immunohistochemical stains for the above markers were performed on paraffin-embedded tissues from 42 de novo DLBCL patients. Median follow-up in all patients was 41 months (range, 1-103 months) and in surviving patients was 65 months (range, 14-103 months). These cases could be classified into three expression patterns: GC B-cell pattern (pattern A) expressing CD10 and/or Bcl-6 but not activation markers; activated GC B-cell pattern (pattern B) expressing at least one of GC B-cell markers and one of activation markers; and activated non-GC B-cell pattern (pattern C) expressing MUM1/IRF4 and/or CD138 but not GC B-cell markers. Patients with pattern A had much better overall survival than those with the other two patterns (Kaplan-Meier survival analysis, P < 0.008, log rank test). Using multivariate Cox proportional hazards regression analysis, the international prognostic index scores and the expression pattern of these markers were independent prognostic indicators. Our results suggest that expression patterns of this panel of GC B-cell and activation markers by immunohistochemistry correlate with the prognosis of patients with DLBCL. Immunohistochemical analysis on paraffin-embedded tissues is more readily available than gene expression profiling by cDNA microarray and may provide similar prognostic information.
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PMID:Immunohistochemical expression patterns of germinal center and activation B-cell markers correlate with prognosis in diffuse large B-cell lymphoma. 1508 65

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

Plasmablastic lymphoma is an aggressive neoplasm that shares many cytomorphologic and immunophenotypic features with plasmablastic plasma cell myeloma. However, plasmablastic lymphoma is listed in the World Health Organization (WHO) classification as a variant of diffuse large B-cell lymphoma. To characterize the relationship between plasmablastic lymphoma and plasmablastic plasma cell myeloma, we performed immunohistochemistry using a large panel of B-cell and plasma cell markers on nine cases of plasmablastic lymphoma and seven cases of plasmablastic plasma cell myeloma with and without HIV/AIDS. The expression profiles of the tumor suppressor genes p53, p16, and p27, and the presence of Epstein-Barr virus (EBV) and human herpes virus type 8 (HHV-8) were also analyzed. All cases of plasmablastic lymphoma and plasmablastic plasma cell myeloma were positive for MUM1/IRF4, CD138, and CD38, and negative for CD20, corresponding to a plasma cell immunophenotype. PAX-5 and BCL-6 were weakly positive in 2/9 and 1/5 plasmablastic lymphomas, and negative in all plasmablastic plasma cell myelomas. Three markers that are often aberrantly expressed in cases of plasma cell myelomas, CD56, CD4 and CD10, were positive in 5/9, 2/5, and 6/9 plasmablastic lymphomas, and in 3/7, 1/5, and 2/7 plasmablastic plasma cell myelomas. A high Ki-67 proliferation index, overexpression of p53, and loss of expression of p16 and p27 were present in both tumors. No evidence of HHV-8 infection was detected in either neoplasm. The only significant difference between plasmablastic lymphoma and plasma cell myeloma was the presence of EBV-encoded RNA, which was positive in all plasmablastic lymphoma cases tested and negative in all plasma cell myelomas. In conclusion, most cases of AIDS-related plasmablastic lymphoma have an immunophenotype and tumor suppressor gene expression profile virtually identical to plasmablastic plasma cell myeloma, and unlike diffuse large B-cell lymphoma. These results do not support the suggestion in the WHO classification that plasmablastic lymphoma is a variant of diffuse large B-cell lymphoma.
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PMID:Plasmablastic lymphomas and plasmablastic plasma cell myelomas have nearly identical immunophenotypic profiles. 1557 69

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

We immunohistochemically defined the histogenesis of posttransplantation lymphoproliferative disorders (PTLDs; B-cell phenotype) occurring after allogeneic T cell-depleted hematopoietic stem cell transplantation (HSCT; n = 15) or solid organ transplantation (SOT; n = 11) to determine whether transplantation type or morphologic subtype of PTLD affected the histogenetic subtype. Immunohistochemical stains using histogenetic markers for germinal center (GC) B cells, late GC and post-GC B cells, and post-GC B cells were performed on paraffin-embedded samples. Morphologically, 14 cases were polymorphic; 12 were monomorphic. Histogenetic marker expression was as follows: 1 monomorphic case (4%), GC phenotype expressing bcl-6 and CD10; 17 cases (65%; polymorphic, 9; monomorphic, 8), late GC-early post-GC phenotype expressing MUM1/IRF4; 8 cases (31%; polymorphic, 5; monomorphic, 3), post-GC phenotype expressing MUM1/IRF4 and CD138 but not bcl-6. PTLD cases after HSCT more frequently were post-GC phenotype than after SOT (7/15 vs 1/11, respectively; P = .040) and were independent of morphologic subclassification. Results suggest that most PTLDs are late GC-early post-GC phenotype with a minor group of post-GC phenotype and rare cases of GC phenotype. Findings also suggest a correlation between histogenetic phenotype of B-cell PTLD and type of transplantation.
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PMID:Histogenetic phenotypes of B cells in posttransplant lymphoproliferative disorders by immunohistochemical analysis correlate with transplant type: solid organ vs hematopoietic stem cell transplantation. 1576 85

This study was undertaken to analyze the differentiation profiles assessed by immunophenotyping in AIDS-related B-cell lymphoma (ARL) and their relation to the clinical course. Paraffin-embedded sections of 89 ARL cases during 1989 to 2004 were stained immunohistochemically with antibodies to CD3, CD10, CD20, CD38, CD138/Syndecan-1 (Syn-1), multiple myeloma-1/interferon regulatory factor-4 (MUM1/IRF4), B-cell lymphoma protein-2 (BCL-2), BCL-6, latent membrane protein-1 (LMP-1), and Ki-67. Expression of CD10 and CD20 were associated with better overall survival (OS; P = .009 and P = .04, respectively). Expression of CD20 was associated with longer disease-free survival (DFS; P = .03), whereas expression of CD138/Syn-1 was associated with shorter DFS (P = .03). OS and DFS were worse in patients with immunophenotypic profiles related to post-germinal center (GC) differentiation (BCL-6 and CD10 negative, MUM1/IRF4 and/or CD138/Syn-1 positive) when compared with GC differentiation (P = .01). When controlled for age-adjusted International Prognostic Index (IPI), prior AIDS-defining illness (ADI), and year of ARL diagnosis, a post-GC differentiation remained significantly associated with poor OS and DFS. Expression of CD10 was associated with a preserved immunocompetence, whereas CD20 was less frequent in patients developing ARL while on highly active antiretroviral therapy (P = .04). In summary, lack of CD20 or CD10 expression and a post-germinal center signature are associated with a worse prognosis in ARL.
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PMID:AIDS-related B-cell lymphoma (ARL): correlation of prognosis with differentiation profiles assessed by immunophenotyping. 1590 93

The human germinal-center-associated lymphoma (HGAL) gene and its cognate protein are expressed in a germinal center (GC)-specific manner. Its expression in classic Hodgkin lymphoma (cHL) prompted us to address whether HGAL expression could distinguish biologically distinct subgroups of cHL. Tissue microarrays from 145 patients treated with curative intent showed HGAL staining in 75% and was closely correlated with MUM1/IRF4 (92%) expression. BCL6 (26%), CD10 (0%), BCL2 (31%), Blimp1 (0.02%), and Epstein-Barr virus (EBV) (20%) showed no specific correlation; neither did phospho-STAT6, a key mediator of IL-4 and IL-13 signaling that induces HGAL and is implicated in cHL pathogenesis. In our study cohort, the 5-year overall survival (OS) correlated with young age (less than 45 years, P < .001), low stage (stage I and II, P = .04), and low International Prognostic Score (P = .002). In univariate analysis, HGAL expression was associated with improved OS (P = .01) and failure-free survival (FFS) (P = .05) but was not independent of other factors in multivariate analysis of OS or FFS. The expression of the GC-specific marker HGAL in a subset of cHL suggests that these cHLs retain characteristics of GC-derived lymphomas. The association with improved OS in univariate but not multivariate analysis suggests that HGAL expression is related to known clinical parameters of improved survival.
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PMID:Expression of the human germinal center-associated lymphoma (HGAL) protein identifies a subset of classic Hodgkin lymphoma of germinal center derivation and improved survival. 1695 3

We previously developed a multivariate model based on the RNA expression of 6 genes (LMO2, BCL6, FN1, CCND2, SCYA3, and BCL2) that predicts survival in diffuse large B-cell lymphoma (DLBCL) patients. Since LMO2 emerged as the strongest predictor of superior outcome, we generated a monoclonal anti-LMO2 antibody in order to study its tissue expression pattern. Immunohistologic analysis of over 1200 normal and neoplastic tissue and cell lines showed that LMO2 protein is expressed as a nuclear marker in normal germinal-center (GC) B cells and GC-derived B-cell lines and in a subset of GC-derived B-cell lymphomas. LMO2 was also expressed in erythroid and myeloid precursors and in megakaryocytes and also in lymphoblastic and acute myeloid leukemias. It was rarely expressed in mature T, natural killer (NK), and plasma cell neoplasms and was absent from nonhematolymphoid tissues except for endothelial cells. Hierarchical cluster analysis of immunohistologic data in DLBCL demonstrated that the expression profile of the LMO2 protein was similar to that of other GC-associated proteins (HGAL, BCL6, and CD10) but different from that of non-GC proteins (MUM1/IRF4 and BCL2). Our results warrant inclusion of LMO2 in multivariate analyses to construct a clinically applicable immunohistologic algorithm for predicting survival in patients with DLBCL.
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PMID:The oncoprotein LMO2 is expressed in normal germinal-center B cells and in human B-cell lymphomas. 1703 24


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