Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:Q96S42 (nodal)
 22,877 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Epstein-Barr virus (EBV) infection is highly associated with specific subtypes of malignant lymphoma. In our previous report on nodal malignant lymphoma in Thailand, we found that 64% of classical Hodgkin's lymphoma (cHL), 51% of non-Hodgkin's lymphoma, T-cell (NHL-T), and 13% of non-Hodgkin's lymphoma, B-cell (NHL-B) were EBV-related. In the present research, we conducted a retrospective study of primary extranodal non-Hodgkin's lymphoma of the sinonasal tract (e-NHL-ST) and primary extranodal non-Hodgkin's lymphoma of the nasopharynx (e-NHL-NP) in Southern Thailand, between 1997 and 2004. EBV-encoded RNA (EBER) expression by in situ hybridization was performed in all cases and a T-cell receptor (TCR)-g gene rearrangement study was performed in NHL-T cases. There were 18 cases of e-NHL-ST and 42 cases of e-NHL-NP detected by histologic and immunohistochemistry examinations. The percentages of e-NHL-ST and e-NHL-NP as compared to nodal malignant lymphoma were 3.7% and 6.8%, respectively. Sixteen cases (88.9%) of e-NHL-ST and 7 cases (16.7%) of e-NHL-NP were NHL-T, and the remainder were NHL-B. All of the NHL-T cases in both sites were EBER-positive. Two (5.4%) of the NHL-B cases in the nasopharynx showed EBER positive. Monoclonal bands of the TCR-gamma gene were detected in 71.4% of the extranodal NK/T-cell lymphomas, nasal type, patients; 50.0% of peripheral T-cell lymphoma, unspecified, patients; and one case of angioimmunoblastic T-cell lymphoma. This study indicates a very strong association of NHL-T in the sinonasal tract or nasopharynx with EBV infection, the link apparently being weaker in NHL-B patients. The study also indicates that most cases of extranodal NK/T-cell lymphoma, nasal type, are not the germline configuration of the TCR genes.
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PMID:Epstein-Barr virus-associated extranodal non-Hodgkin's lymphoma of the sinonasal tract and nasopharynx in Thailand. 1662 23

The germinal center T-helper cell has been proposed as the cell of origin for angioimmunoblastic T-cell lymphoma. Our recent report of expression of CXCL13, a chemokine critical for germinal center formation and one of the most highly upregulated genes in the germinal center T-helper cell subset, in the majority of angioimmunoblastic T-cell lymphoma cases, provided further support for this theory. To determine the specifity of this marker for angioimmunoblastic T-cell lymphoma, we evaluated CXCL13 expression in 26 nodal-based peripheral T-cell lymphomas and 14 lymph nodes showing paracortical lymphoid hyperplasia. No significant paracortical CXCL13 staining was seen in the reactive lymph nodes. By WHO classification criteria, 20 of the lymphoma cases were considered peripheral T-cell lymphoma, unspecified, and six were reclassified as angioimmunoblastic T-cell lymphoma after immunohistochemical detection of disorganized follicular dendritic cell meshworks. Combining the results of our studies, 31 of 35 angioimmunoblastic T-cell lymphoma cases (89%) showed CXCL13 expression, in contrast to two out of 20 peripheral T-cell lymphoma, unspecified cases (10%). The two peripheral T-cell lymphoma, unspecified cases that were positive for CXCL13 showed a Lennert lymphoma-like histology. While these cases did not meet all histologic criteria for angioimmunoblastic T-cell lymphoma, they did show an increase in EBV-positive B cells, suggesting they may be histologic variants of angioimmunoblastic T-cell lymphoma. In conclusion, CXCL13 expression is a distinctive feature of angioimmunoblastic T-cell lymphoma, providing further support for the germinal center T-helper cell as the cell of origin for this neoplasm. Given its specificity when compared to cases of peripheral T-cell lymphoma, unspecified as well as paracortical lymphoid hyperplasia, it may be a useful marker in the diagnosis of angioimmunoblastic T-cell lymphoma.
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PMID:Expression of CXCL13, a chemokine highly upregulated in germinal center T-helper cells, distinguishes angioimmunoblastic T-cell lymphoma from peripheral T-cell lymphoma, unspecified. 1668 Jan 56

The first classifications deviding B- and T-cell lymphomas were given with the Kiel classification and in the classification of Lukes and Collins. Those entities first described like T-zone lymphomas or T-CLL are the rarest types of the known entities today. The updated Kiel classification contained a large number of especially nodal peripheral T-cell lymphomas and seperated lymphoblastic ones from those which derive from peripheral T-cells. The increasing knowledge on T-cell differentiation allowed a more detailed description of entities according either to their primary organ manifestation (subcutaneous panniculitis-like T-cell lymphoma), their immunophenotype (NK/T-cell lymphomas with expression of CD56) or their rearrangement of the T-cell receptor (predominantly gamma/sigma-rearrangement in hepatosplenic T-cell lymphoma). The today's nodal and extranodal NK/T-cell lymphoma entities are summarized by the WHO classification. They can be seperated in primary leukemic ones, primary nodal ones, primary extranodal and primary cutaneous ones. In extranodal sites some lymphoma entities show a characteristic picture which is unique for this localisation. It has become clear that morphology alone is not able to lead to a reproducable classification of T-cell lymphomas. Today immunhistochemistry together with the distinct primary organ localisation are the major tools for classifying peripheral NK/T-cell lymphomas. In this paper distinct examples which are interesting in the differential diagnosis or which are distinct clinico-pathological entities are described. Moreover, an indication is given on some new rare entities which have not yet been listed in the WHO classification.
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PMID:[Classification and differential diagnosis of NK/T-cell lymphomas]. 1688 93

Peripheral T-cell lymphomas (PTLs) are uncommon, accounting for fewer than 10% of all non-Hodgkin lymphomas. Success in therapy of the PTLs has lagged behind that of aggressive B-cell lymphomas, and most PTLs have a poor prognosis. The molecular pathogenesis of most PTLs is also poorly understood. In the WHO classification, clinical features, in conjunction with morphological and immunophenotypic criteria, are relied on to define most disease entities. Functionally, T-cell lymphomas are related to the two major arms of the immune system, the innate and adaptive immune systems. NK cells and T cells of the innate immune system recognize antigen in the absence of MHC antigens and are involved in mucosal immunity. The lymphomas derived from these cells often involve cutaneous and mucosal sites. The expression of cytotoxic molecules in these lymphomas may predispose to apoptosis by tumor cells and normal bystander cells. Hepatosplenic T-cell lymphoma is a systemic disease derived from functionally immature innate effector cells, most often of gammadelta T-cell origin. In contrast, most nodal T-cell lymphomas belong to the adaptive immune system. Angioimmunoblastic T-cell lymphoma (AILT) is mostly likely derived from follicular helper T-cells (T(FH)), a finding that explains many of its pathological and clinical features. Studies of these neoplasms may assist in further unraveling the functional diversity of their normal counterparts.
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PMID:Pathobiology of peripheral T-cell lymphomas. 1712 78

CD52 antigen (Campath-1) is expressed in high density by lymphocytes and monocytes. Campath-1H or alemtuzumab, a human anti-CD52, has been shown to be effective in T-cell malignancies; however, there is very limited information on CD52 expression in T-cell lymphoma (TCL). This study retrospectively investigated 97 TCL cases by immunohistochemistry using paraffin sections to elucidate the CD52 expression rates in various TCL sub-types. Fourteen cases of angioimmunoblastic T-cell lymphoma (AITL) were excluded as there were no reliable criteria to differentiate whether the CD52-positive cells were neoplastic T-cells, which are usually small-sized, or the usually abundant, small-to-large residual/reactive B-cells in this lymphoma sub-type. In the remaining 83 tumors, CD52 was expressed in 29 (35%) tumors including 8/17 (47%) NK/T-cell lymphomas, 14/35 (40%) unspecified peripheral TCLs and 4/18 (22%) anaplastic large cell lymphomas. There was no statistical significance in CD52 expression in terms of patient age, gender, nodal vs extra-nodal presentation or tumor sub-types. The authors recommend performing CD52 immunostaining for future clinical trials of alemtuzumab on TCL patients and to correlate the staining results with treatment outcome.
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PMID:CD52 expression in non-mycotic T- and NK/T-cell lymphomas. 1732 55

Given their relative rarity, one of the primary diagnostic difficulties in nodal T-cell lymphomas is recognizing their range of histologic patterns. This is complicated by the fact that most mature T-cell lymphomas retain some functional characteristics of nonneoplastic T cells, ie, the capacity to secrete cytokines and costimulate immune cell growth, and, thus, are associated with obscuring nonneoplastic immune cells. Sessions 2 and 3 of the Society for Hematopathology/European Association for Haematopathology Workshop focused on these issues and conditions that may simulate T-cell lymphomas. We summarize salient features of presented cases, including the varied patterns seen in angioimmunoblastic T-cell lymphoma (AITL) and other more poorly characterized morphologic and functional nodal T-cell lymphoma subsets. Many cases illustrated the difficulties distinguishing AITL from peripheral T-cell lymphoma, unspecified, when the neoplasms manifest only some AITL features. The usefulness of separately classifying T-cell lymphomas that demonstrate follicular, perifollicular, or T-zone patterns of infiltration; significance of immunophenotypically distinct subsets that express cytotoxic markers or have features of central memory T cells; diagnostic difficulties posed by B-cell proliferations that accompany T-cell lymphomas; and T-cell lymphoma mimics related to genetic disorders, immune dysregulation, and drug reactions are also discussed.
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PMID:Morphologic and immunophenotypic variants of nodal T-cell lymphomas and T-cell lymphoma mimics. 1736 27

Cutaneous lymphomas are rare skin diseases. They must be differentiated from secondary skin infiltrates by primary nodal lymphomas. Primary cutaneous lymphomas can be classified into B- and T-cell lymphomas and hematodermic neoplasms; they usually possess a favorable prognosis and run a chronic course. Treatment is dependent on stage. As complete cure is not possible, it is essential to control the disease and alleviate symptoms. In recent years numerous new drugs have been developed to treat these diseases.
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PMID:Cutaneous lymphomas. 1761 Jun 12

F-18-fluoro-deoxy-glucose positron emission tomography (PET) is highly sensitive and specific in the imaging of B-cell lymphomas. In contrast, its utility in the diagnostic evaluation of T-cell lymphomas is less defined. In this article, we present our finding utilizing PET in peripheral T-cell lymphomas (PTCL). A retrospective review of patients who underwent PET examinations at our institution produced 24 PET examinations among patients with PTCL. A lesion-based analysis was undertaken to evaluate the diagnostic accuracy of PET in PTCL. PET findings were compared with a standard of reference and sensitivity, specificity, positive and negative predictive values were calculated. PET had an overall sensitivity of 86% and specificity of 100%. PET had high sensitivity (95%) at nodal and non-cutaneous extra-nodal sites and poor sensitivity (13%) at cutaneous sites. The mean SUV of abnormal foci in anaplastic large cell lymphoma was 11 mg/ml (range: 3 - 40), and PTCL-unclassified was 8 mg/ml (range: 1 - 23).
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PMID:F-18-fluoro-deoxy-glucose positron emission tomography in the assessment of peripheral T-cell lymphomas. 1770 74

Zanolimumab is a human IgG1 antibody against CD4, which is in clinical development for the treatment of cutaneous and nodal T-cell lymphomas. Here, we report on its mechanisms of action. Zanolimumab was found to inhibit CD4+ T cells by combining signaling inhibition with the induction of Fc-dependent effector mechanisms. First, T-cell receptor (TCR) signal transduction is inhibited by zanolimumab through a fast, dual mechanism, which is activated within minutes. Ligation of CD4 by zanolimumab effectively inhibits early TCR signaling events but, interestingly, activates signaling through the CD4-associated tyrosine kinase p56lck. An uncoupling of p56lck from the TCR by anti-CD4 allows the kinase to transmit direct inhibitory signals via the inhibitory adaptor molecules Dok-1 and SHIP-1. Second, CD4+ T cells are killed by induction of antibody-dependent cell-mediated cytotoxicity, to which CD45RO+ cells are more sensitive than CD45RA+ cells. Finally, zanolimumab induces down-modulation of CD4 from cell surfaces via a slow Fc-dependent mechanism. In conclusion, zanolimumab rapidly inhibits T-cell signaling via a dual mechanism of action combined with potent Fc-dependent lysis of CD4+ T cells and may act long-term by down-regulating CD4.
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PMID:A human CD4 monoclonal antibody for the treatment of T-cell lymphoma combines inhibition of T-cell signaling by a dual mechanism with potent Fc-dependent effector activity. 1794 27

CD20 positive T-cell lymphoma is extremely rare. Most reported cases are nodal peripheral T-cell lymphomas (PTCLs) or rarely lymphoma involving extranodal sites. Only two cases of CD20 positive T-cell lymphomas involving the skin have been previously reported and were classified as PTCL - not otherwise specified. We present a case report of a 53-year-old man with CD20 positive mycosis fungoides (MF) involving the skin and an inguinal lymph node. The patient presented with erythematous patches and plaques of the right lower extremity and was found to have an enlarged inguinal lymph node 2 years later. Flow cytometric immunophenotyping of the lymph node aspirate showed a CD2+/CD3+/CD4+/CD5+/CD7-/CD8- T-cell population with CD20 co-expression. Molecular studies by polymerase chain reaction demonstrated clonal T-cell receptor gamma chain gene rearrangement. Immunoglobulin heavy and light chain gene rearrangements were not identified. To our knowledge, this is the first case of CD20 positive MF involving a lymph node to be reported in the literature.
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PMID:CD20 positive mycosis fungoides: a case report. 1826 Nov 16


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