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)

Anaplastic large cell lymphoma (ALCL) and Hodgkin lymphoma (HL) express CD30 at high levels, but stimulation of this molecule has been reported to induce contradictory effects. To elucidate the molecular mechanism of CD30-mediated apoptosis of ALCL, we compared the gene expression profiles of t(2;5)(p23;q35)-positive ALCL with those of HL altered by CD30 agonistic stimulation. The results showed that BCL3, the high-level expression of which in ALCL was previously reported, was further upregulated in response to CD30 stimulation, along with several pro-apoptotic genes. Bcl-3 protein was present as an intermediate phospho-form in the resting-state ALCL, becoming hyperphosphorylated (Bcl-3P) upon stimulation. We next found that the stimulation promoted de novo synthesis of the nuclear factor (NF)-kappaB2/p100 precursor as well as processing to p52, and a series of immunoprecipitation and western blotting analyses consistently showed association of Bcl-3P with p52 in CD30-stimulated ALCL. An electrophoretic mobility shift assay revealed the induction of kappaB binding activity of the p52 homodimer, and nuclear colocalization of Bcl-3 and p52 was demonstrated in anaplastic lymphoma kinase-positive ALCL tumor tissues by immunohistochemistry. As Bcl-3 can act as an anti-repressor or transactivator or both, we propose that the (p52)2/Bcl-3P ternary complex, which is specifically induced in CD30-stimulated ALCL, can modulate expression of apoptosis-related genes regulated by NF-kappaB, thereby accounting for CD30-mediated apoptosis of ALCL.
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PMID:Stimulation of CD30 in anaplastic large cell lymphoma leads to production of nuclear factor-kappaB p52, which is associated with hyperphosphorylated Bcl-3. 1610 30

High expression of CD30 and JunB is characteristic of tumor cells in anaplastic large cell lymphoma (ALCL) and Hodgkin lymphoma (HL). Possible interactions of CD30 and JunB were examined in this study. We found that the CD30 promoter in tumor cells of both nucleophosmin (NPM)-anaplastic lymphoma kinase (ALK)-positive and NPM-ALK-negative ALCL and HL is regulated by a constitutively active CD30-extracellular signal-regulated kinase (ERK) 1/2 mitogen-activated protein kinase (MAPK). Phosphorylation of ERK1/2 MAPK was confirmed in nuclei of tumor cells in both ALCL and HL. CD30-ERK1/2 MAPK signals induce JunB expression, which maintains high activity of the CD30 promoter. JunB induction seems to be largely independent of nuclear factor kappaB in ALCL and HL. These results show a common mechanism of CD30 overexpression in ALCL and HL, although the outcome of CD30 signaling differs between NPM-ALK-positive ALCL and NPM-ALK-negative ALCL, cutaneous ALCL, and HL as we recently reported.
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PMID:JunB induced by constitutive CD30-extracellular signal-regulated kinase 1/2 mitogen-activated protein kinase signaling activates the CD30 promoter in anaplastic large cell lymphoma and reed-sternberg cells of Hodgkin lymphoma. 1614 Sep 28

Anaplastic large cell lymphoma (ALCL) comprises 10-15% of childhood non-Hodgkin lymphomas (NHL). Systemic ALCL is highly associated with anaplastic lymphoma kinase (ALK) gene translocations with over-expression of ALK protein. We studied ALK rearrangements using fluorescence in situ hybridisation (FISH) and ALK immunohistochemical staining in 43 paediatric systemic ALCLs. FISH (performed on 35 cases) identified a translocation in 29 cases (83%). Immunohistochemistry identified ALK over-expression in 42/43 cases (97%) with the single ALK-negative case demonstrating an ALK rearrangement by FISH, indicating 100% incidence of ALK translocations.
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PMID:Childhood anaplastic large cell lymphoma has a high incidence of ALK gene rearrangement as determined by immunohistochemical staining and fluorescent in situ hybridisation: a genetic and pathological correlation. 1635 38

Peripheral T-cell lymphomas (PTCLs) represent a heterogeneous group of non-Hodgkin's lymphomas. With few exceptions (eg, anaplastic large-cell lymphoma expressing the anaplastic lymphoma kinase), PTCLs have generally been reported to have a worse prognosis compared with B-cell lymphomas. Despite the poor outcome after conventional therapy, the impact of high-dose therapy with autologous or allogeneic stem cell transplantation (SCT) in these rare diseases is poorly defined mainly because of the lack of prospective PTCL-restricted studies. Most data exist for high-dose therapy with autologous SCT in relapsing or refractory disease. Because most studies showed similar results for PTCL compared with aggressive B-cell lymphomas in which high-dose therapy with autologous SCT is accepted as standard therapy, this approach seems appropriate in relapsing or refractory PTCL. Results for high-dose therapy with autologous SCT as first-line therapy mainly rely on studies on aggressive lymphomas that also included lymphomas of the T-cell phenotype. Our own recently published PTCL-restricted prospective study confirmed the feasibility with only moderate toxicity and a good response rate. Overall, patients with a good remission status after induction therapy exhibited a high complete response rate after transplantation, and at least a subgroup of patients remained in long-term remission. The greatest uncertainty exists for the impact of allogeneic SCT after high-dose therapy. In refractory or relapsing PTCL, this approach might improve the outcome for eligible patients, especially when using reduced-intensity conditioning. Overall, because data on high-dose therapy for PTCL are limited, larger and randomized studies are necessary to definitely confirm the preliminary results.
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PMID:The role of high-dose therapy in peripheral T-cell lymphomas. 1664 Aug 12

There is a diagnostic grey zone between classic Hodgkin lymphoma (cHL) and some non-Hodgkin lymphoma (NHL), including primary mediastinal B cell lymphoma, diffuse large B cell lymphoma, and anaplastic large cell lymphoma. They all have some morphological and/or phenotypic features in common. To investigate this, we undertook an expression profiling study of these lymphomas using comparative expressed sequence hybridization. This technique detects chromosomal regions that are differentially expressed between a test and a reference tissue in a manner similar to comparative genomic hybridization, and is particularly suitable when the number of informative biopsies is limited. Using this approach, we identified a unique expression profile for all lymphoma types investigated. Unsupervised hierarchical cluster analysis of the acquired data showed that cHL separates from all investigated NHLs, including ALCL-like HL. Moreover, anaplastic lymphoma kinase (ALK)-negative ALCL clustered in a separate branch together with ALCL-like HL. Thus, analysing the neoplastic cells concurrently with their microenvironment, ALK-negative ALCL and ALCL-like HL seem to be related to each other, while cHL constitutes a separate lymphoma entity.
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PMID:Relationship between classic Hodgkin lymphoma and overlapping large cell lymphoma investigated by comparative expressed sequence hybridization expression profiling. 1687 43

Anaplastic large cell lymphoma (ALCL) comprises approximately 25 % of all non-Hodgkin lymphomas in children and young adults. 40% of these tumours have a translocation t(2;5)(p23;q35), which fuses the nucleophosmin gene (NPM) to the anaplastic lymphoma kinase gene (ALK) resulting in a hybrid protein which contributes to the pathogenensis of ALCL. To further analyse the transforming activity in an animal model, a cDNA encoding the protein product, NPM-ALK, was incorporated into a retrovirus construct and introduced into mouse bone marrow progenitors by infection. In a bone marrow gene transfer and transplantation protocol the hematopoietic compartments of lethally irradiated IL-9 transgenic mice were reconstituted with npm-alk infected progenitor cells. IL-9 transgenic mice were chosen, because IL-9, a pleiotropic T helper 2 cytokine, is expressed in most cases of human ALCL and was shown to have an oncogenic potential at least on T cells. Reconstituted mice developed NPM-ALK positive lymphomas including lymphoblastic lymphomas of T-cell type (T-LB), mature and immature plasmacytoma (PZ) and plasmoblastic/anaplastic diffuse large B-cell lymphoma after 10-30 weeks. The combined overexpression of NPM-ALK and IL-9 exerts cooperative oncogenic activity in the transformation of murine lymphoid cells leading to accelerated and enhanced development of T-LB. Many animals developed plasmacytic/plasmoblastic neoplasms, of which the most aggressive tumours share many features with human anaplastic/plasmoblastic diffuse large B-cell lymphoma.
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PMID:[Overexpression of NPM-ALK induces different types of malignant lymphomas in IL-9 transgenic mice]. 1688 16

Cellular Jun (c-Jun), a member of the JUN family, is an activator protein-1 transcription factor involved in cell differentiation, proliferation, and apoptosis that can be activated by phosphorylation at serine-73 and -63 residues. Using tissue microarrays and immunohistochemistry, we investigated c-Jun expression and serine-73 phosphorylation in 112 CD30 lymphomas and 232 CD30 lymphomas of B- or T-cell lineage, and 24 cases of lymphomatoid papulosis. c-Jun was expressed exclusively by CD30 lymphoproliferative disorders including 41/41 (100%) classical Hodgkin lymphoma (cHL), 20/23 (87%) anaplastic lymphoma kinase (ALK)+ anaplastic large cell lymphoma (ALCL), 18/26 (69%) ALK- ALCL, 5/9 (56%) primary cutaneous ALCL, 4/11 (36%) CD30 diffuse large B-cell lymphoma (DLBCL), and 11/24 (46%) cases of lymphomatoid papulosis. The percentage of c-Jun-positive tumor cells was highest in cHL and ALCL (P=0.002). In contrast, all CD30 lymphomas, including nodular lymphocyte predominant HL and CD30 non-Hodgkin lymphomas of B- or T-cell lineage were negative for c-Jun. Serine-73 phosphorylated c-Jun (p-c-Jun), the activated form of c-Jun, was expressed more frequently and at a higher level in cHL and ALK+ ALCL than other CD30 tumors. The percentage of p-c-Jun-positive tumor cells correlated significantly with the percentage of total c-Jun-positive cells (P<0.0001), suggesting that activated c-Jun positively regulates total c-Jun levels in CD30 lymphomas through a well-established positive feedback loop. We conclude that CD30 lymphomas are characterized by common patterns of c-Jun expression and activation suggesting a potential role of c-Jun in the pathogenesis of these tumors.
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PMID:c-Jun expression and activation are restricted to CD30+ lymphoproliferative disorders. 1732 87

Session 8 of the 2005 Society of Hematopathology/European Association for Haematopathology Workshop was devoted to anaplastic large cell lymphoma (ALCL). Most cases submitted were anaplastic lymphoma kinase (ALK)+ ALCL highlighting unusual clinical settings, histologic variants, and variant translocation partners. Cases submitted as ALK- ALCL emphasized the immunohistochemical overlap with classical Hodgkin lymphoma (eg, CD15+/CD30+). It was also clear that consensus histologic and immunohistochemical criteria for the diagnosis of ALK-ALCL are lacking. Many expressed the opinion that ALK-ALCL is not a distinct entity at the immunophenotypic or genetic level and is better designated as peripheral T-cell lymphoma (PTCL), unspecified. Others suggested that the histologic features of ALK-ALCL are distinctive nevertheless and that this diagnosis has meaning that is lost by designating these neoplasms as PTCL, unspecified. This session also included CD30+ anaplastic lymphomas involving skin in which the differential diagnosis included cutaneous ALCL and systemic ALK-ALCL.
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PMID:Anaplastic Large Cell Lymphoma. 1751 Nov 13

Anaplastic large cell lymphoma (ALCL) comprises a group of non-Hodgkin lymphomas characterized by the expression of the CD30/Ki-1 antigen. A subset of ALCL is characterized by chromosomal translocations involving the anaplastic lymphoma kinase (ALK) gene on chromosome 2. While the most common translocation is the t(2;5)(p23;q35) involving the nucleophosmin (NPM) gene on chromosome 5, up to 12 other translocations partners of the ALK gene have been identified. One of these is the t(1;2)(q25;p23) which results in the formation of the chimeric protein TPM3-ALK. While several of the signaling pathways induced by NPM-ALK have been elucidated, those involved in ALCLs harboring TPM3-ALK are largely unknown. In order to investigate the expression profiles of ALCLs carrying the NPM-ALK and TPM3-ALK fusions, we carried out cDNA microarray analysis of two ALCL tissue samples, one expressing the NPM-ALK fusion protein and the other the TPM3-ALK fusion protein. RNA was extracted from snap-frozen tissues, labeled with fluorescent dyes and analyzed using cDNAs microarray containing approximately 9,200 genes and expressed sequence tags (ESTs). Quantitative fluorescence RT-PCR was performed to validate the cDNA microarray data on nine selected gene targets. Our results show a significant overlap of genes deregulated in the NPM-ALK and TPM-ALK positive lymphomas. These deregulated genes are involved in diverse cellular functions, such as cell cycle regulation, apoptosis, proliferation, and adhesion. Interestingly, a subset of the genes was distinct in their expression pattern in the two types of lymphomas. More importantly, many genes that were not previously associated with ALK positive lymphomas were identified. Our results demonstrate the overlapping and unique transcriptional patterns associated with the NPM-ALK and TPM3-ALK fusions in ALCL.
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PMID:Analysis of gene expression profile of TPM3-ALK positive anaplastic large cell lymphoma reveals overlapping and unique patterns with that of NPM-ALK positive anaplastic large cell lymphoma. 1772 Feb 43

Anaplastic large cell lymphoma (ALCL) designates a heterogeneous group of CD30+ (systemic or primary cutaneous) peripheral T-cell lymphomas (PTCLs). A subgroup of systemic ALCL is transformed by anaplastic lymphoma kinase (ALK). We compared 46 ALCL with 22 PTCLs in terms of T-cell receptor (TCR) rearrangements, expression of TCRs and TCR-associated molecules [CD3, ZAP-70 (zeta-associated protein 70)]. Despite their frequent clonal rearrangement for TCRbeta, only 4% of ALCLs expressed TCRbeta protein, whereas TCRs were detected in 86% of PTCLs. Moreover, both TCRbeta+ ALCLs lacked CD3 and ZAP-70 (ie, molecules indispensable for the transduction of cognate TCR signals). Defective expression of TCRs is a common characteristic of all types of ALCL, which may contribute to the dysregulation of intracellular signaling pathways controlling T-cell activation and survival. This molecular hallmark of ALCL is analogous to defective immunoglobulin expression distinguishing Hodgkin lymphoma from other B-cell lymphomas.
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PMID:[Anaplastic large cell lymphomas lack the expression of T-cell receptor molecules]. 1803


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