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 MALT1 gene was identified through its involvement in t(11;18)(q21;q21), seen in 30% of cases of mucosa-associated lymphoid tissue (MALT) lymphoma. Here, we show that deregulated MALT1 expression may occur in B-cell non-Hodgkin lymphoma (B-NHL) of various histologic subtypes either through translocation to the immunoglobulin heavy chain (IGH) locus or by genomic amplification. First, 2 cases, one case of MALT lymphoma and another of aggressive marginal zone lymphoma (MZL) with t(14;18)(q32;q21), cytogenetically identical to the translocation involving BCL2, were shown by fluorescence in situ hybridization (FISH) to involve MALT1, which lies about 5 Mb centromeric of BCL2. Molecular cloning of both by long-distance inverse polymerase chain reaction showed breakpoints lying 1 to 2 kilobase (kb) centromeric of the first 5' MALT1 exon; both cases showed MALT1 overexpression at either RNA or protein levels. Second, we examined the structure and gene expression profile of genomic amplifications involving 18q21 in a panel of 40 B-NHL cell lines using comparative genomic hybridization to microarrays (array CGH) and gene expression profiling techniques. Using array CGH, 2 peaks of genomic amplification were observed, one centered around BCL2 and the other around MALT1. Ofthe 3 cell lines with MALT1 amplification, 2 showed MALT1 overexpression as assessed by gene profiling, quantitative reverse transcription-polymerase chain reaction (QRT-PCR), and Western blotting. To determine if comparable events occurred in primary MALT and splenic MZL tumors, 40 cases were analyzed by FISH or QRT-PCR; genomic amplification and MALT1 overexpression were seen in 2 cases. Together, these data implicate MALT1 as a dominant oncogene that may play a role in the pathogenesis of B-NHL.
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PMID:MALT1 is deregulated by both chromosomal translocation and amplification in B-cell non-Hodgkin lymphoma. 1256 Feb 19

DNA amplifications are important mechanisms for proto-oncogene activation. Comparative genomic hybridization (CGH) to metaphase chromosome preparations has revealed amplifications in 10-20% of B-cell lymphomas (B-NHL). We analysed a series of 16 aggressive non-Hodgkin lymphomas by the new approach termed Matrix-CGH (M-CGH) using genomic DNA microarrays as hybridization target. For M-CGH, a dedicated B-cell lymphoma chip was constructed containing 496 genomic targets covering oncogenes, tumor suppressor genes as well as chromosome regions frequently altered in B-NHL. In 10 of 16 samples a total of 15 DNA amplifications were identified. The amplicons included BCL2, REL, CCND1, CCND2, JAK2, FGF4 and MDM2. Four of the 15 amplifications remained undetected by chromosomal CGH. The respective amplicons mapped to bands 2p13, 9p13-p21 and 12q24 and, were confirmed by fluorescence in situ hybridization. Furthermore, for four genomically amplified genes real-time quantitative reverse transcription polymerase chain reaction revealed elevated mRNA expression levels. These data show the superior diagnostic sensitivity of the newly developed diagnostic tool. As only a small portion of the genome (approximately 1.5%) has been analysed by the present DNA array, it is likely that gene amplifications are much more common in aggressive lymphomas than previously assumed.
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PMID:Hidden gene amplifications in aggressive B-cell non-Hodgkin lymphomas detected by microarray-based comparative genomic hybridization. 1261 69

Cytogenetic analysis including multicolor spectral karyotyping (SKY) and interphase fluorescence in situ hybridization (FISH) was performed on 154 consecutive cases with suspected lymphoma. The cytogenetic results were reviewed in correlation with the final pathologic diagnosis. A diagnosis of lymphoma was established in 94 cases, with 16 Hodgkin lymphomas and 78 non-Hodgkin lymphomas (NHL). Cytogenetic results were obtained in 63 NHLs (81%); 61 of those showed abnormal karyotypes (97%). The t(14;18) or IGH-BCL2 fusion was detected in 83% (20/24) of follicular lymphomas and in 57% (12/21) of diffuse large B-cell lymphomas (DLBCL). The application of interphase FISH and SKY has contributed to a high detection rate of t(14;18) in DLBCLs. This study showed that genes at 1q25, 3p21, 3q21, 5q31, 6p23, 7q22, 8q11 approximately q12, 9q34, 11q23, 12q13, and 19q13.1 may have been involved as the less common changes in follicular lymphoma and DLBCL. Comparison of the recurrent secondary aberrations in the groups of follicular lymphoma and DLBCL revealed a pattern of clonal evolution from the changes rea(1)(p36), del(6q), +7, +12 or dup or trp(12)(q13q22), +der(18)t(14;18), and +21 in follicular lymphoma to the changes rea(1)(p36), del(6q), +6, +7, +9, rea(11)(q23), +12, -13 or del(13(q12q14), +18, +21, and +X in DLBCL. The clonal evolution of the secondary aberrations is thought to contribute to the progression of the disease. About 90% (16/18) of other types of NHL had abnormal karyotypes showing specific translocations or gene rearrangements consistent with the pathologic diagnosis. A comprehensive cytogenetics approach including SKY and interphase FISH using probes for specific genes, such as IGH, BCL2, CCND1, and ALK, is a very useful ancillary diagnostic tool for lymphomas. The combined approach also led to the identification of t(2;19)(p23;q13.1) as a new variant of t(2;5)(p23;q35) in a case of Ki-1-positive anaplastic large cell lymphoma with a null cell phenotype.
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PMID:Comprehensive cytogenetic analysis including multicolor spectral karyotyping and interphase fluorescence in situ hybridization in lymphoma diagnosis. a summary of 154 cases. 1274 58

Occasionally, primary large B-cell lymphomas (LBLs) arising in the spleen present with a micronodular pattern involving the splenic white pulp but sparing the red pulp. Histologically, the nodules contain scattered large B cells in a background of numerous T cells and histiocytes. They can cause substantial difficulty in histologic diagnosis as the morphology can mimic reactive and inflammatory lesions as well as other lymphoid neoplasms. In this study, we examined the histology and immunophenotype of the micronodular T-cell/histiocyte-rich LBL (MTLBL) of the spleen with a view to establish the characteristics that may be helpful in diagnosis. Paraffin-embedded material from 17 cases of MTLBL was studied. Clinical features and histology were reviewed and immunohistochemistry was performed for immunoglobulins, CD20, CD79a, CD3, CD68, CD10, BCL6, BCL2, OCT-2, epithelial membrane antigen, CD30, CD138, and EBV markers. The median age of presentation was 56 years, and the most frequent presenting features were anemia and B symptoms. All cases showed a micronodular pattern of involvement. The tumor nodules comprised a mixture of numerous CD3+ T cells and CD68+ histiocytes and scattered large CD20+ B cells with immunoglobulin light chain restriction. They were positive for BCL6 and OCT2 but negative for CD10, CD138, and EBV markers. There was variable expression of epithelial membrane antigen, Bcl-2, and CD30. No follicle dendritic cell meshwork infrastructure underlying the nodules could be demonstrated by staining for CD21 or CD35 antigens. The prognosis was poor; seven of the 12 cases with follow-up were dead within 2 years. MTLBL is unique variant of T-cell/histiocyte-rich diffuse LBL, characterized by primary splenic presentation and a micronodular architecture. The main differential diagnoses include granulomatous inflammation, Hodgkin's lymphoma, follicular lymphoma, and peripheral T-cell lymphomas.
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PMID:Micronodular T-cell/histiocyte-rich large B-cell lymphoma of the spleen: histology, immunophenotype, and differential diagnosis. 1282 82

Mantle cell lymphoma (MCL) is an aggressive subentity of non-Hodgkin lymphoma (NHL), responds poorly to therapy, is resistant to current therapeutic strategies and has the shortest survival of all lymphoma entities. The blastoid variant of mantle cell lymphoma (MCL-BV) has an even worse clinical outcome. The mechanisms of neoplastic transformation from normal mantle cells and the relationship to the rare blastoid variant are poorly understood. BCL2 is overexpressed in indolent B-cell NHL including MCL. In addition, other proteins of the BCL-family are overexpressed in MCL like BCLX, whereas the expression of BAX and BAK was not elevated in MCL. BCL2 independent apoptotic pathways are altered in MCL. CD40, which can mediate B-cell survival, is overexpressed in MCL. Furthermore, the expression of FAS which is known to be pro-apoptotic is markedly decreased favoring the CD40 mediated cell survival pathway in these cells. Besides overexpression of cyclin D1, the cyclin dependent kinases (CDK2 and CDK4) are highly expressed in MCL resulting in the phosphorylation of RB1, E2F release, and the cell cycle progression. The new technique of gene expression analysis by microarrays promotes more insight into the pathogenesis of MCL and discovery of altered cell signaling pathways, and the ability to predict subgroups of patients with different risk and probability of response to treatment.
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PMID:Altered apoptosis pathways in mantle cell lymphoma. 1506 Nov 96

Diffuse large B-cell lymphoma (DLBCL), the most common subtype of adult non-Hodgkin lymphoma (NHL), is infrequently seen in adolescents and is rare in children. Due to the infrequency of the disease, single institution-based cytogenetic and fluorescence in situ hybridization (FISH) studies of pediatric DLBCL have not been reported so far and, hence, the possible differences in pediatric and adult DLBCL have not been evaluated. We performed cytogenetic and FISH analyses of 7 pediatric and 5 young adult DLBCL cases referred to the University of Nebraska Medical Center. Karyotypic studies revealed numeric and structural chromosome abnormalities in all cases. Loss of chromosomes 2, 3, 4, 6, 12, 15, 16, and 17, and gain of 12, 18, and X were observed in more than 20% of the cases (#10878;3 cases). Sex chromosome abnormalities and cytogenetically unidentifiable chromosomes and/or segments were observed in 80% (10/12) of the cases. Recurrent breakpoints (observed in 3 or more cases) included 14q32 (IGH) and 17p13 (TP53), which clustered in the young adult group. The breakpoints 7q36, 9p24, 13q34, and 16q24 were noted in two cases each. We performed interphase FISH studies to verify the possible rearrangements of the breakpoints that are frequently implicated in adult DLBCL. Our results confirmed that the pediatric cases did not show rearrangements of 3q27 (BCL6), 14q32 (IGH), 18q21 (BCL2), 8q24 (CMYC), and 17p13 (TP53), except for one case with IGH;BCL2 dual fusion [t(14;18)(q32;q21)] and one with a 17p13 (TP53) deletion. Although 3q27 was noted to be rearranged by conventional cytogenetics in two young adult DLBCL cases, FISH investigations verified that BCL6 was not disrupted. The t(8;14)(q24;q32) with rearranged CMYC ascertained by FISH, was observed in a single young adult DLBCL case. These results highlight a distinctly different representation of cytogenetic abnormalities in pediatric versus adult DLBCL.
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PMID:Cytogenetics and fluorescence in situ hybridization studies of diffuse large B-cell lymphoma in children and young adults. 1535 Mar

Primary effusion lymphoma (PEL) is a unique form of non-Hodgkin lymphoma (NHL) associated with Kaposi sarcoma-associated herpesvirus (KSHV; HHV-8) that displays a distinct constellation of clinical, morphologic, immunologic, and molecular characteristics. Rare KSHV-containing immunoblastic lymphomas occurring in solid tissues have been described. Whether they represent part of the spectrum of PEL has not been determined. The morphologic, immunophenotypic, and molecular features of KSHV-positive solid lymphomas occurring in 8 HIV+/AIDS patients were systematically investigated and compared with those of 29 similarly analyzed PELs. The 8 KSHV-positive solid lymphomas were virtually indistinguishable from the 29 PELs based on morphology (immunoblastic/anaplastic), immunophenotype (CD45 positive; T cell antigen negative; CD30, EMA, CD138 positive; CD10, CD15, BCL6 negative) and genotype (100% immunoglobulin genes rearranged; no identifiable abnormalities in C-MYC, BCL6, BCL1, BCL2; and uniformly EBV positive). The only identifiable phenotypic difference was that the KSHV-positive solid lymphomas appeared to express B cell-associated antigens (25%) and immunoglobulin (25%) slightly more often than the PELs (<5% and 15%, respectively; P = 0.11 and P = 0.08, respectively). The clinical presentation and course of the patients who develop KSHV-positive solid lymphomas were also similar, except for the lack of an effusion and somewhat better survival (median 11 months vs. 3 months). However, the 3 KSHV-positive solid lymphoma patients alive without disease 11, 25, and 44 months following initial presentation were recently diagnosed patients and, unlike the other patients with KSHV-positive solid lymphomas, received anti-retroviral therapy. These findings strongly suggest that these decidedly rare KSHV-positive solid lymphomas belong to the spectrum of PEL. Therefore, we propose that the KSHV-positive solid lymphomas be designated extra-cavitary PELs.
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PMID:KSHV-positive solid lymphomas represent an extra-cavitary variant of primary effusion lymphoma. 1548 44

Molecular cytogenetic techniques enabled us to clarify numerical and structural alterations previously detected by conventional cytogenetic techniques in 37 patients who had myelodysplastic syndromes with complex karyotypes. Using high-resolution comparative genomic hybridization (HR-CGH), we found the most recurrent alterations to be deletion of 5q (70%), 18q (35%), 7q (32%), 11q (30%), and 20q (24%), gain of 11q (35%) and 8q (24%), and trisomy of chromosome 8 (19%). Furthermore, in 35% of the patients, 20 amplifications were identified. These amplifications were shown by FISH to involve some genes previously described as amplified in hematological malignancies, such as ERBB2, MLL, and RUNX1. In addition, two other genes, BCL6 and BCL2, which are classically related to apoptosis and non-Hodgkin lymphoma, were shown for the first time to be involved in amplification. Genomic alterations involving different subtelomeric regions with losses in 4p16, 5p15.3, 6q27, 18p11.3, and 18q23 and gains in 1p36.3 and 19p13.3 were detected by HR-CGH. Array CGH analysis of the subtelomeric regions in some samples was able to confirm a number of these alterations and found some additional alterations not detected by conventional CGH.
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PMID:Analysis of myelodysplastic syndromes with complex karyotypes by high-resolution comparative genomic hybridization and subtelomeric CGH array. 1561 30

The BCL-2 family has been implicated in the pathogenesis of various hematopoietic malignancies, including follicular non-Hodgkin lymphoma and B-cell chronic lymphocytic leukemia. To identify genes that act synergistically in BCL2-enforced leukemogenesis, we developed a murine B-cell lymphoma/leukemia model based on the IL-3-dependent Balb/C pro-B line (FL5.12). FL5.12 cells were stably transfected with antiapoptotic BCL-2 alone or in combination with proapoptotic BAX or nonfunctional mutant BAX, thereby creating various levels of imbalance within the BCL-2 family. Transfectants were intravenously injected into normal Balb/C mice. Whereas FL5.12 cells did not provoke leukemia, mice injected with stable transfectants died of leukemia over time. Disease incidence and latency time depended on the degree of imbalance in the BCL-2 family, supporting a model whereby BCL2 drives tumorigenesis. All mice presented with hepatosplenomegaly and leukemic FL5.12 cells in peripheral blood and bone marrow compartments. Leukemic conversion was accompanied by secondary genetic aberrations leading to clonal IL-3-responsive leukemia. Cellular transformation was independent of alterations in c-Myc or downstream apoptotic pathway. Leukemic clones retained a normal DNA damage response leading to elevated P53 and P21 levels and cell cycle arrest upon irradiation. In conclusion, our mouse model may prove a valuable tool to identify genes that cooperate in BCL2-enforced lymphoma/leukemogenesis.
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PMID:Novel murine B-cell lymphoma/leukemia model to study BCL2-driven oncogenesis. 1564 25

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


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