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) is a neoplasm of activated lymphocytes, commonly expressing T-cell antigens and cytotoxic proteins. Histopathology reveals distinctive infiltration of sinuses and paracortical T-cell-rich regions of lymph nodes by tumor cells which have abundant cytoplasm and large irregular/convoluted nuclei, and which are frequently multinucleated with prominent nucleoli. ALCL often presents in advanced clinical stages with B symptoms; extranodal disease occurs in 40% of patients. The pathogenesis of systemic ALCL is linked to phosphorylation of a tyrosine kinase (ALK) resulting in unregulated growth of affected lymphoid cells. ALK is activated through chromosomal translocations/inversions with any of several partner genes, most commonly nucleophosmin (NPM). Downstream signal transduction pathway(s) are not fully defined but appear to involve phospholipase Cgamma, phosphatidylinositol (PI)3K/Akt, and STAT-3 and STAT-5 proteins. Primary cutaneous ALCL appears to have a different pathogenesis and better prognosis than does systemic ALCL, presenting as one or more skin tumors, usually localized. Excision or local irradiation is usually effective treatment. A clinically benign variant of primary cutaneous ALCL is lymphomatoid papulosis (LyP), characterized by recurrent crops of papules/nodules up to 2 cm in diameter which undergo spontaneous regression. LyP is managed by observation, ultraviolet light therapy, or low-dose methotrexate. LyP patients have a predisposition to develop malignant lymphomas, including Hodgkin's lymphoma, mycosis fungoides, and non-Hodgkin's lymphoma, by as yet unknown mechanisms. The prognosis for patients with LyP is otherwise excellent.
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PMID:Systemic and primary cutaneous anaplastic large cell lymphomas. 1287 73

We studied whether signaling through CD30, a member of the TNF receptor family, affected acute infection with HIV-1, encompassing its entire replicative cycle. Several non-Hodgkin cell lines, targets of CXCR4-dependent (X4) HIV-1 infection, were positive for CD30 expression. CD30 ligation induced up-regulation of viral replication only in certain CD30+ cell lines. Enhancement of X4 virus replication by CD30 engagement inversely correlated with both CD30 surface density and constitutive NF-kappaB activation. Conversely, expression of CD30, but not of other members of the TNF receptor family, was proportional to constitutive NF-kappaB binding. Concomitantly, secretion of soluble (s) CD30 increased in all cell lines by CD30 ligation. sCD30 release was enhanced by engagement of CD30 alone and, to a greater extent, by co-engagement of CD3 also in primary gamma delta T lymphocytes, along with complementary modulations of their surface CD30 expression. sCD30-containing supernatant specifically inhibited HIV-1 expression induced by CD30 engagement in chronically infected ACH-2 T cells; thus sCD30 may act as a negative feed-back molecule. In conclusion, we have delineated novel features of CD30 biology and underline the peculiar link of CD30 expression to constitutive NF-kappaB activation which is pivotal to both HIV replication and cell survival.
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PMID:CD30 ligation differentially affects CXCR4-dependent HIV-1 replication and soluble CD30 secretion in non-Hodgkin cell lines and in gamma delta T lymphocytes. 1457 82

In a previous study, we showed that the high level of protein tyrosine phosphorylation present in lymphomas containing an anaplastic lymphoma kinase (ALK) can be demonstrated in routinely processed paraffin tissue sections using immunolabelling techniques. In the present study we investigated whether oncogenic tyrosine kinase activation also occurs in other categories of lymphoma by staining 145 cases of lymphoma covering those tumours with a range of different subtypes including those with morphological similarity to ALK-positive anaplastic large cell lymphoma (ALCL). Twelve cases of the borderline malignant disorder lymphomatoid papulosis were also studied. Twenty seven of the 28 cases of ALK-positive ALCL showed the extensive cytoplasmic labelling for phosphotyrosine in the neoplastic cells. The remaining case containing moesin-ALK exhibited membrane-associated phosphotyrosine expression. There was no nuclear phosphotyrosine labelling in any of the ALK-positive ALCL, even though ALK was present within the cell nuclei in 23 of the tumours. Variable degrees of phosphotyrosine labelling, usually membrane-restricted, were observed in 7/40 cases of ALK-negative ALCL, 9/29 cases of diffuse large B-cell lymphoma, 3/6 cases of mediastinal B-cell lymphoma, 2/7 cases of Hodgkin's lymphoma, 3/6 cases of peripheral T-cell lymphomas unspecified, 4/6 cases of B-cell chronic lymphocytic leukaemia, 2/6 cases of follicular lymphomas and 2/12 cases of lymphomatoid papulosis studied. However none of these phosphotyrosine-positive cases showed the strong cytoplasmic labelling comparable to that seen in ALK-positive lymphoma. We conclude that activation of a tyrosine kinase is probably not a major oncogenic event in lymphomas other than ALK-positive ALCL.
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PMID:Tyrosine phosphorylation in human lymphomas. 1462 44

Anaplastic large cell lymphomas (ALCLs) represent a heterogeneous group of malignant lymphoproliferative diseases. Most of the cases are of T-cell line with a loss of cell surface receptors but with a production of cytotoxic cytoplasmatic granules--immunohistochemically (IHC) positive perforin, granzyme B, and TIA-1. The diagnostics of ALCL is based on morphological findings and results of IHC, which further stratify ALCLs to basic immunophenotypes according to ALK (anaplastic lymphoma kinase) protein expression--ALCL CD30+ ALK+ and ALCL CD30+ ALK+. The morphological investigations are supplemented by karyotyping and/or by a demonstration of breakpoint at 2p23 harboring ALK gene (FISH), and by molecular detection of chimeric genes characteristic of ALK+ lymphomas (NPM-ALK, ATIC-ALK, TPM3-ALK, TFG-ALK, and some even rarer rearrangements). Molecular diagnostics is important in monitoring minimal residual disease. As some of the characteristic molecular changes were demonstrated in healthy individuals and in Hodgkin's disease by quantitative PCR, the validation of these findings demands further studies. ALK protein positive ALCLs affect patients in age categories up to the third decade, whereas ALK protein negative cases occur in older patients with an average age of 60 years. Both subgroups of lymphomas are aggressive but ALK+ lymphomas react well to systemic treatment, and have a more favorable prognosis. Primary skin ALCLs belong to a group of T-cell lymphoproliferative diseases of the skin and have, in the majority of cases, a favorable course without generalization.
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PMID:[Anaplastic large-cell lymphoma: review]. 1463 6

Anaplastic large cell lymphoma (ALCL) is a subgroup of non-Hodgkin's lymphomas with large lymphoma cells expressing CD30 antigen. This entity has rarely been reported in Taiwan. We performed a retrospective clinicopathologic study in a medical center in southern Taiwan during a 13-year period and identified 13 cases. There were 10 males and 3 females with a median age of 49 years old. Seven presented with pure nodal disease and 5 had bony involvement. The staging results were stage I (5 patients), II (1), III (1), and IV (4). The pathologic subtypes were common variant (10), lymphohistiocytic variant (2), and small cell variant (1). Eleven tumors were of T-cell lineage; 2, null-cell. Immunohistochemically, 5 tumors (38.5%) expressed cytotoxic markers, T-cell intracellular antigen-1 and/or granzyme B. Two tumors (15.4%) expressed anaplastic lymphoma kinase (ALK). Long-term follow-up information was available in 8 patients. The 2 patients with ALK-expressing tumors (37 and 49 years old) were free of disease for 61 and 54 months, respectively. The other 6 patients were either died of disease (5 patients) or experienced relapse with progressive disease (1). In conclusion, we reported the largest series of ALCL in Taiwan. We confirmed ALK-expressing ALCL carries favorable prognosis and ALK-negative ALCL has similar poor prognosis as non-anaplastic T-cell lymphoma. As compared to the previous reports from the West, our ALK positive rate was lower and the age of our ALK-positive patients was older. A larger national or multi-institutional study is needed for further characterization of ALCL in Taiwan.
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PMID:Anaplastic large cell lymphoma--a rare disorder in southern Taiwan. 1469 25

Anaplastic large cell lymphoma is a unique diagnostic subcategory of the T-cell lymphomas in the current World Health Organization classification. Representing approximately 3% of adult and 10% to 30% of childhood non-Hodgkin lymphomas, anaplastic large cell lymphoma classically consists of CD30+ large lymphoid cells with abundant cytoplasm and pleomorphic, often horseshoe-shaped or kidney-shaped nuclei. Among the reported nodal and extranodal sites of occurrence, the gastrointestinal tract and central nervous system have rarely been noted. We report a case of primary anaplastic lymphoma kinase-negative anaplastic large cell lymphoma in the brain of a 46-year-old patient with acquired immunodeficiency syndrome. T-cell lineage was confirmed by T-cell receptor gamma chain gene rearrangements using polymerase chain reaction, and extra copies of the anaplastic lymphoma kinase gene of chromosome 2 were demonstrated by fluorescence in situ hybridization analysis. To our knowledge, primary anaplastic large cell lymphoma of the brain has not previously been reported in acquired immunodeficiency syndrome.
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PMID:Primary anaplastic lymphoma kinase-negative anaplastic large cell lymphoma of the brain in a patient with acquired immunodeficiency syndrome. 1498 53

NPM-ALK characterizes anaplastic large cell lymphoma (ALCL), as does the high expression of CD30, a feature shared with H-RS cells of classic Hodgkin's lymphoma. In H-RS cells, ligand-independent signaling by overexpressed CD30 drives constitutive NF-kappaB activation, which is absent in ALCL cells. Here we show that NPM-ALK impedes CD30 signaling and NF-kappaB activation, dependent on both ALK kinase activity and the N-terminal NPM domain. NPM-ALK transduction into H-RS cell lines abrogates recruitment and aggregation of TRAF proteins, inducing an ALCL-like morphology and phenotype. TRAF2 associates with NPM-ALK at a consensus binding motif located in the kinase domain. Thus, NPM-ALK abrogates CD30-driven NF-kappaB activation and can also induce an ALCL phenotype, distinguishing ALCL cells from H-RS cells of T cell origin.
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PMID:The NPM-ALK oncoprotein abrogates CD30 signaling and constitutive NF-kappaB activation in anaplastic large cell lymphoma. 1509 42

c-Kit receptor (CD117) is expressed by erythroid, megakaryocytic, and myeloid precursors and mature mast cells and has been reported to be expressed in CD30+ lymphomas such as Hodgkin's disease and anaplastic large-cell lymphoma. Imatinib mesylate, a well-established inhibitor of bcr-abl tyrosine kinase, and currently used for the treatment of patients with chronic myeloid leukemia, also inhibits c-kit receptor kinase activity. In view of the possible use of imatinib as experimental therapy for patients with c-kit-positive tumors, we assessed c-kit expression in CD30+ cell lines and lymphomas. The cell lines were assessed using multiple methods (RT-PCR, flow cytometry, and Western blot). c-Kit expression was also immunohistochemically assessed in 168 CD30+ lymphomas including 87 classical Hodgkin's disease, 63 anaplastic large-cell lymphoma, and 15 cutaneous anaplastic large-cell lymphoma. We also studied 18 cases of lymphomatoid papulosis, a CD30+ lesion closely related to cutaneous anaplastic large-cell lymphoma. Neither c-kit mRNA nor protein was detected in any of the cell lines assessed. Furthermore, treatment with imatinib did not inhibit proliferation of cell lines in vitro. Using immunohistochemistry, only one of 183 (0.5%) lesions was positive for c-kit, the positive case being an ALK-negative anaplastic large-cell lymphoma. Our data demonstrate that expression of c-kit receptor is exceedingly rare among CD30+ lymphomas and lymphomatoid papulosis, suggesting that c-kit receptor is unlikely to be an appropriate target for therapeutic options such as imatinib in patients with these tumors.
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PMID:Lack of c-kit (CD117) expression in CD30+ lymphomas and lymphomatoid papulosis. 1510 13

The frequency of Epstein-Barr virus (EBV) in anaplastic large cell lymphoma (ALCL) has been controversial. The interpretation of previous studies is complicated by the use of nonuniform EBV detection methods and the inclusion of cases of CD30-positive diffuse large B-cell lymphoma and so-called "ALCL, Hodgkin-like," as defined in the Revised European-American Lymphoma classification scheme. In the current World Health Organization (WHO) classification system, both of these tumors are excluded from the ALCL category. Also, recently developed antibodies (eg, the antibody specific for PAX-5/B-cell-specific activator protein [BSAP]) provide new, sensitive tools for identifying neoplasms of B-cell lineage that can morphologically resemble ALCL. In this study we evaluated 64 cases of ALCL of T- or null-cell lineage, defined according to the WHO classification system, for the presence of EBV. All tumors were negative for B-cell antigens, including PAX-5/BSAP and CD20 or CD79a. The study group included 27 (42%) anaplastic lymphoma kinase (ALK)-positive (18 T-cell and 9 null-cell) and 37 (58%) ALK-negative (30 T-cell and 7 null-cell) tumors analyzed by in situ hybridization for EBV-encoded RNA (EBER) or immunohistochemistry for EBV-latent membrane protein type 1. All 64 cases were negative for EBV. We conclude, based on the current definition of ALCL in the WHO classification, there is no role for EBV in ALCL arising in Western patients. We suggest that published reports of EBV in a small proportion of ALCL cases in Western patients can be explained by the inclusion of tumors no longer considered to be in the current classification of ALCL, such as CD30-positive anaplastic tumors of B-cell origin.
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PMID:Absence of Epstein-Barr virus in anaplastic large cell lymphoma: a study of 64 cases classified according to World Health Organization criteria. 1511 26

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 24 ALK(+), 15 ALK(-) systemic, and 7 cutaneous ALCLs with 29 nonanaplastic 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 2 (4%) of 47 ALCLs expressed TCRbeta protein, whereas TCRs were detected on 27 of 29 nonanaplastic 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 or molecules of proximal T-cell receptor signaling. 1529 16


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