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)

In the present study, we show by Northern blot analysis and enzyme linked immunosorbent assay that the Hodgkin's disease (HD)-derived cell lines HDLM-2 and KM-H2 express a variety of cytokine genes either constitutively or upon induction with phorbol ester 12-O-tetradecanoylphorbol-13-acetate. Cytokine genes expressed by HD-derived lines include granulocyte-macrophage colony-stimulating factor (CSF), macrophage-CSF, interleukin (IL)-1-alpha, IL-3, IL-5, IL-6, IL-8, leukemia inhibitory factor, tumor necrosis factor-alpha, tumor necrosis factor-beta, and transforming growth factor-beta, while transcripts and the corresponding proteins for granulocyte-CSF, IL-1-beta, IL-2, IL-4, IL-7, IL-10, and the JE/macrophage chemoattractant and activating factor gene were not detectable in cytoplasmic RNA and culture supernatants obtained from both lines. In addition, IL-2 receptor (R) p55 and macrophage-CSF R (c-fms) genes were expressed by both lines. HDLM-2, but not KM-H2 cells, exhibited the IL-6 R p80 and the IL-2 R p75 chain. Analysis of nuclear proteins that bind to oligonucleotides containing the consensus sequences of the transcription factors activation protein 1, nuclear factor (NF) kappa B, and NFAT 1 revealed a pattern for HD lines resembling that of activated T-cells: HDLM-2 and KM-H2 cells constitutively expressed NF binding to the NF of activated T-cells (type 1), previously described to be T-cell specific. In addition, NF kappa B-binding proteins obtained from both lines showed, in electrophoretic mobility shift assays, the same migration pattern as T-cell-derived proteins but differed from monocyte- and B-cell-derived proteins. UV cross-linking experiments confirmed that NF kappa B-binding proteins of M(r) 85,000, 75,000, and 50,000/55,000 were detectable in nuclear extracts obtained from T-cells and both HD lines, while monocytes and B-cells displayed the M(r) 50,000/55,000 and 75,000 NF kappa B complex only. Both HD lines also constitutively expressed transcripts for c-fos and c-jun, which are involved in heterodimeric formation of the transcription factor activation protein 1, as well as for the NF kappa B/KBF1 gene.
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PMID:Expression of cytokine genes, cytokine receptor genes, and transcription factors in cultured Hodgkin and Reed-Sternberg cells. 159 93

The p80(NPM/ALK) expression activated by the t(2;5) (p23;q35) translocation recently has been shown to play an important role in the pathogenesis of anaplastic large cell lymphoma (ALCL). However, the clinicopathologic significance of identification of p80 among ALCL cases has not been completely resolved. Difficulties also exist in the histologic and immunophenotypic identification of ALCL and Hodgkin's disease (HD) as separate processes, often complicating the clinicopathologic evaluation of and therapeutic approach to these entities. In order to clarify these issues, 67 specimens of ALCL and 63 specimens of HD (31 of the nodular-sclerosing type [NS-HD] and 32 of the mixed-cellularity type [MC-HD]) were immunostained using anti-p80 antibody and other relevant markers on paraffin sections. The clinicopathologic and immunophenotypic features were reviewed on the basis of p80 reactivity. The expression of p80 was detected in 43 of 67 cases of ALCL (64%), but none of HD. The p80+ ALCL cases constituted a very homogeneous group of tumors, characterized by the occurrence in a much younger group and relatively more favorable clinical course than the p80- ALCL, which were in keeping with the data previously reported. They showed virtually the identical immunophenotypic findings of p80+, CD30+, EMA+, CD15-, bcl-2-, and Epstein-Barr virus (EBV) with T- and null-cell phenotype, and showed the distinct morphologic features, including three cases of lymphohistiocytic/small-cell variant, as follows: the indented nuclei, often termed as reniform, embryolike, and horseshoelike; multiple, irregular, but indistinct nucleoli; and few reactive cells of eosinophils and epithelioid cells. Conversely, the 24 p80- ALCL cases, in which epithelial membrane antigen (EMA) and bcl-2 positivities were 33% and 55%, respectively, were heterogeneous and could be subdivided into five different categories, namely (a) 11 cases of HD-like ALCLs, (b) six cases of p80 common ALCL, (c) three cases of secondary ALCL, (d) two cases of primary cutaneous ALCL, and (e) two cases of primary classical ALCL that lacked p80 expression. This study clearly demonstrated that the immunohistochemical detection of p80 is of a crucial importance in delineating the biologically distinct entity of "primary classical ALCL" from various diseases that show morphologic and immunohistologic overlap, including HD and HD-like ALCL.
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PMID:Anaplastic large cell lymphoma: a distinct molecular pathologic entity: a reappraisal with special reference to p80(NPM/ALK) expression. 941 85

The t(2;5) (p23;q35) chromosomal translocation is found in about 40% of lymph node-based CD30+ anaplastic large cell lymphomas of T-cell or null-cell lineage. This translocation results in the expression of a fusion protein containing the catalytic domain of anaplastic lymphoma kinase (ALK) under the control of the promoter for nucleophosmin (NPM), a nucleolar phosphoprotein. Expression of ALK activity, normally absent in lymphocytes, is postulated to be involved in the pathogenesis of lymphomas bearing the t(2;5) translocation. Certain primary cutaneous lymphoproliferative disorders and Hodgkin's disease are also known to contain CD30+ large lymphoid cells. In order to determine the role of the t(2;5) translocation in these diseases, several investigators have employed a variety of techniques including cytogenetics, genomic Southern blot analysis, RNA- and DNA-based PCR assays, various forms of in-situ hybridization, and immunostaining for the p80 fusion protein encoded by the chimeric t(2;5) transcripts. These studies included approximately 415 cases of Hodgkin's disease, 65 cases of CD30+ primary cutaneous large cell lymphoma, and 38 cases of lymphomatoid papulosis. The aggregate results of these studies indicate that the t(2;5) translocation or other somatic mutations resulting in inappropriate expression of ALK are involved rarely if at all in the pathogenesis of Hodgkin's disease, but may be present in about 10% of cases of lymphomatoid papulosis and 20% of cases of CD30+ primary cutaneous large cell lymphoma. However, the t(2;5) has not been detected yet in any case involving multiple or secondary CD30+ lymphoproliferative disorders, thereby providing no evidence for a role in tumor clone progression. Additional studies will be needed to determine if t(2;5) status has any clinical significance for patients with CD30+ primary cutaneous lymphoproliferative disorders.
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PMID:Analysis of the t(2;5) (p23;q35) translocation in CD30+ primary cutaneous lymphoproliferative disorders and Hodgkin's disease. 963 79

A recurrent, reciprocal balanced translocation, t(2;5) (p23;q35), has been recognized in CD30+ anaplastic large-cell lymphomas (ALCL), a newly recognized subtype comprising approximately 5% of all non-Hodgkin's lymphoma (NHL). This translocation creates a novel fusion protein, NPM-ALK, which has transforming properties in vitro and can cause large-cell lymphoma in vivo when transfected into murine bone marrow. Multiple techniques including reverse transcriptase-polymerase chain reaction (RT-PCR) amplification of NPM-ALK fusion transcripts, genomic DNA-PCR, RNA in situ hybridization, and fluorescence in situ hybridization (FISH) of metaphase chromosomes and interphase nuclei, and immunohistochemical detection of the 80 kilodalton protein (p80) derived from the NPM-ALK fusion have enabled surveys of normal and lymphoma tissues for evidence of the translocation. These studies suggest that expression of ALK protein, a novel orphan receptor tyrosine kinase, is normally confined to the nervous system. In lymphoma, NPM-ALK expression is most often seen in young patients with the monomorphic or small-cell variant of ALCL who present with advanced stage disease and have tumors with a CD30+, T- or null-cell phenotype. It is less frequently detected in older patients and in ALCL of pleomorphic histology. In addition, expression of NPM-ALK has been found in occasional CD30 negative B-cell lymphomas with diffuse large cell or immunoblastic histology. NPM-ALK is rarely, if ever, detected in Hodgkin's disease or secondary ALCL. Although initially found in primary nodal ALCL, recent studies suggest that NPM-ALK expression may occur in lymphoma at extranodal sites, including the skin; it remains controversial, however, whether CD30+ primary cutaneous lymphoma and its benign counterpart, lymphomatoid papulosis (LyP), express NPM-ALK in some cases. A retrospective study has suggested that expression of NPM-ALK is associated with a better overall 5-year survival; these results must be confirmed in prospective studies of patients with uniform staging and therapy to more fully understand the clinical significance of the t(2;5) and its novel chimeric protein, NPM-ALK.
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PMID:The t(2;5) in human lymphomas. 968 23

Anaplastic large cell lymphomas (ALCL) are a heterogeneous group of CD30+ large cell lymphomas; the most characteristic type have a T or null cell phenotype, often express epithelial membrane antigen (EMA) and cytolytic lymphocyte markers, and often possess a nonrandom t(2;5)(p23;q35) chromosomal translocation. We studied 22 (19 T, 1 null, 2 B cell) ALCL, including four primary cutaneous ALCL (PC-ALCL), for the expression of TIA-1, the cytotoxic T lymphocyte (CTL) or natural killer (NK) cell-associated antigens CD4, CD8, betaF1, TCRdelta1, CD56, and CD57, the ALCL-associated antigens p80 and EMA, and the Hodgkin's disease-associated marker CD15 to better define the relationship of these markers to histological subtype, primary site, and patient clinical characteristics. TIA-1 expression was seen in 12 of 20 (60%) T or null cell ALCLs with a cytoplasmic, granular distribution. Ultrastructural studies showed cytotoxic-type granules (dense core, multivesicular, and intermediate types) with TIA-1 localized to granules on immunogold labeling. TIA-1 staining strongly correlated with young patient age (< or = 32 years, P < .05) and EMA expression (P < .05). Excluding the four PC-ALCL cases, TIA-1 staining also correlated with p80 expression (P < .05) in all of the T cell cases. Three CD15+ cases were TIA-1-. TIA-1 expression in T or null cell ALCL was seen in all morphological subtypes (2 of 2 small cell variant, 3 of 4 monomorphic variant, and 7 of 14 pleomorphic variant) and primary tumor sites (6 of 14 nodal, 2 of 4 primary cutaneous, 2 of 2 bone, and 2 of 2 soft tissue). TIA-1+ granules were seen in all subsets: 5 of 6 CD4+, 1 of 2 CD8+, 4 of 8 CD56+, and 1 of 2 CD57+ ALCL. Of note, 4 of 10 T or null cell ALCL expressed gammadelta T-cell receptors (TCR), whereas only 1 of 10 T or null cell ALCL was alphabeta TCR+; TCR were not detected in five cases. TIA-1 was expressed by 3 of 4 gammadelta TCR+ ALCL and 1 of 1 alphabeta TCR+ ALCL. These data support a cytotoxic lymphocyte phenotype in most T or null cell ALCL and suggest that some T cell ALCL are derived from cytolytic CD4+ T cells, gammadelta T cells, or NK-like (CD56+ or CD57+) T cells.
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PMID:The expression of TIA-1+ cytolytic-type granules and other cytolytic lymphocyte-associated markers in CD30+ anaplastic large cell lymphomas (ALCL): correlation with morphology, immunophenotype, ultrastructure, and clinical features. 1002 54

The expression of cytotoxic granule-associated proteins has been reported in some T-cell or natural killer (NK)-cell lymphomas of mostly extranodal origin, but rarely of nodal origin except for anaplastic large cell lymphoma (ALCL) and Hodgkin's disease (HD). This study analyzed 66 nodal lymphomas expressing T-cell intracellular antigen-1 (TIA-1) and/or granzyme B to characterize the clinicopathologic spectrum of these neoplasms. Four main groups could be delineated. The first group consisted of p80/anaplastic lymphoma kinase (ALK)-positive ALCL (n = 35). The patients were 2 to 62 years of age (median age, 16 years), and the lymphomas pursued a relatively indolent clinical course. The tumors were phenotypically of either T- or null-cell type with constant expression of CD30, epithelial membrane antigen (EMA), and p80/ALK, but not CD15 or BCL2. None harbored Epstein-Barr virus (EBV). The second group consisted of peripheral T/NK-cell lymphoma, the nodal high-grade cytotoxic type (n = 13). The patients were 29 to 72 years in age (median age, 55 years), and the tumors pursued an aggressive clinical course. The tumors often showed pleomorphic, anaplastic, or centroblastoid morphology, and were featured by either EBV association or CD56 expression. The third group consisted of peripheral T-cell lymphoma, of the nodal low-grade cytotoxic type (n = 8). The patients, three men and five women, were 31 to 75 years old (median age, 61 years). Notably, six of them exhibited lymphoepithelioid (Lennert's) lymphoma. The fourth group consisted of cytotoxic Hodgkin's-like ALCL/HD (n = 10), included seven cases of Hodgkin's-like ALCL and three cases of HD, and was characterized by the presence of Reed-Sternberg cells and often the CD15+ phenotype. The patients were all men except for one woman, and they ranged in age from 24 to 84 years (median age, 62 years). The link among these four groups was reinforced by the presence of a highly characteristic large cell with horseshoelike or reniform nuclei-the frequent expression of CD30 and EMA-and the often lack of T-cell receptor-alphabeta. In this series, the expression of p80/ALK and CD56 was also associated with favorable and poor prognoses respectively (p<0.001, log-rank test).
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PMID:Nodal cytotoxic lymphoma spectrum: a clinicopathologic study of 66 patients. 1097 9

The clinicopathological and biological significance of Hodgkin's disease and non-Hodgkin's lymphoma, which are infrequently encountered in women of childbearing age, remains to be clarified. We recently reviewed 4 cases of non-Hodgkin's lymphoma of the T/natural killer (T/NK)-cell phenotype, all of which were associated with pregnancy and characterized by the expression of the cytotoxic granule-associated proteins T-cell intracellular antigen-1 and/or granzyme B. The 4 cases selected had presented between November 1993 and May 1999. The criteria for selection were that the onset of clinical manifestations occurred during pregnancy or within 6 months after delivery. The patients comprised 1 patient with p80/anaplastic lymphoma kinase (ALK)-positive anaplastic large cell lymphoma (ALCL), 1 with p80/ALK-negative ALCL, and 2 with peripheral T/NK-cell lymphomas of unspecified type. The diseases followed aggressive clinical courses: 3 patients died within 6.5 months after diagnosis, and only 1 was still alive with the disease 17 months after diagnosis. The diseases appeared to progress rapidly after delivery. Maternal immunity and hormonal changes during pregnancy may be closely related to the biological behavior of these unusual tumors. This study is, to the best of our knowledge, the first to address pregnancy-associated cytotoxic lymphoma.
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PMID:Pregnancy-associated cytotoxic lymphoma: a report of 4 cases. 1159 20

Expression of argyrophilic proteins of nucleolar organizers regions (Ag-NOR-proteins) was studied in tumor cells from 17 patients with a classic variant of anaplastic large-cell lymphoma (ALCL) and 22 patients with Hodgkin's lymphoma (HL). Eight cases of p80+ and nine cases of p80-ALCL were studied. HL was represented by 13 cases with lymphoid depletion by a reticular type and 9 cases with nodular sclerosis with a syncytial growth. Ag-NOR-proteins were identified using histochemical method with silver nitrate. The expression of Ag-NOR-proteins in tumor cells of ALCL and HL appeared intensive, being highest in ALCL cells, in p80+ cells of ALCL there was superexpression. The differences in expression of Ag-NOR-proteins point to different proliferative activity and growth of the above variants of ALCL and HL. The test for Ag-NOR-proteins expression can be recommended as an additional tool in differential diagnosis, determination of malignancy grade, assesssment of prognosis and sensitivity to chemotherapy.
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PMID:[Argyrophilic proteins of nucleolar organizers regions as markers of malignancy grade of anaplastic large-cell lymphoma and Hodgkin's lymphoma]. 1557 84

CD26/dipeptidyl peptidase IV is a cell surface antigen with multiple biological functions. Although its involvement in tumor biology has been suggested, the significance of its expression in malignant lymphoma has not been clarified in detail. This study examined the expression of CD26 and cell surface adenosine deaminase (ADA) in 42 cases of Hodgkin's lymphoma (HL) and T-cell lymphoma by immunohistochemistry on frozen sections. CD26 was expressed in three of 14 cases of HL, in four of eight cases of anaplastic large cell lymphoma (ALCL), in two of nine cases of peripheral T-cell lymphoma, in one of six cases of lymphoblastic lymphoma and in none of three cases of adult T-cell lymphoma/leukemia. Expression of cell surface ADA was fully correlated with the expression of CD26 and expression of CD26/ADA in ALCL and HL was also completely correlated with the expression of p80 and epithelial membrane antigen. Of 10 CD26-positive patients, seven had fever and elevated CRP at initial diagnosis and over a median follow-up of 61 months (range, 7 - 152 months) only three survived. This study suggested that CD26 is selectively expressed on ALK-positive, but not on ALK-negative, ALCL and HL. This is also the first report to demonstrate that ADA is coexpressed with CD26 on the cell surface of malignant neoplasms in vivo.
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PMID:CD26, together with cell surface adenosine deaminase, is selectively expressed on ALK-positive, but not on ALK-negative, anaplastic large cell lymphoma and Hodgkin's lymphoma. 1707 93

We report an extremely rare case of interdigitating dendritic cell sarcoma/tumor (IDCS). A 52-year-old man presented with a 2-week history of fever in January 2002. Physical examination revealed enlarged, painless right axillary lymph nodes, and hepatosplenomegaly. Whole-body computerized tomography showed enlarged lymph nodes in mediastinal, right axillary, abdominal para-aortic, ileum, and inguinal regions. Hepatosplenomegaly was also detected. In addition to abnormal liver function tests, serum levels of soluble interleukin-2 receptor and ferritin were elevated. Excisional biopsy of right axillary lymph node was performed in February 2002. Histological examination showed a diffuse proliferation of medium-to large-sized cells with round or oval nuclei and abundant cytoplasm. Spindle shape cells and Hodgkin-like giant cells were also seen. Immunohistochemically, the tumor cells expressed S-100 protein, CD 68, and CD 45 RO. They were negative for CD 1, CD 3, CD 15, CD 20, CD 21, CD 23, FDC, DRC, and p80. These findings were compatible with the diagnosis of IDCS. The patient was treated with polychemotherapy consisting of doxorubicin,cyclophosphamide, vincristine, and prednisone. However, he developed fungal pneumonia and died of respiratory failure 1 month after the start of treatment.
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PMID:[Interdigitating dendritic cell sarcoma/tumor--a case report]. 1735 46


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