Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:Q06643 (non-Hodgkin's lymphoma)
 11,307 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Posttransplantation lymphoproliferative disorders (PT-LPDs) represent a heterogeneous group of Epstein-Barr virus-associated lymphoid proliferations that arise in immunosuppressed transplant recipients. Some of these lesions regress after a reduction in immunosuppressive therapy, whereas some progress despite aggressive therapy. Morphological, immunophenotypic, and immunogenotypic criteria have not been useful in predicting clinical outcome. Although structural alterations in oncogenes and/or tumor suppressor genes identified in some PT-LPDs correlate with a poor clinical outcome, the presence of these alterations has not been a consistently useful predictor of lesion regression after reduction of immunosuppression. We examined 57 PT-LPD lesions obtained from 36 solid organ transplant recipients for the presence of mutations in the BCL-6 proto-oncogene using single-strand conformation polymorphism and sequence analysis, followed by correlation with histopathologic classification and clinical outcome, which was known in 33 patients. BCL-6 gene mutations were identified in 44% of the specimens and in 44% of the patients; none were identified in the cases classified as plasmacytic hyperplasia. However, mutations were present in 43% of the polymorphic lesions and 90% of the PT-LPDs diagnosed as non-Hodgkin's lymphoma or multiple myeloma. BCL-6 gene mutations predicted shorter survival and refractoriness to reduced immunosuppression and/or surgical excision. Our results suggest that the BCL-6 gene structure is a reliable indicator for the division of PT-LPDs into the biological categories of hyperplasia and malignant lymphoma, of which only the former can regress on immune reconstitution. The presence of BCL-6 gene mutations may be a useful clinical marker to determine whether reduction in immunosuppression should be attempted or more aggressive therapy should be instituted.
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PMID:BCL-6 gene mutations in posttransplantation lymphoproliferative disorders predict response to therapy and clinical outcome. 974 67

The incidence of malignant lymphomas is significantly higher in patients who have congenital or acquired immunodeficiencies. Although there are some differences between these immunodeficiency-associated lymphoproliferative disorders (IALD), they share several features: a tendency to present in extranodal sites, particularly the central nervous system and gastrointestinal tract, rapid clinical progression when untreated, diffuse large cell histology, B-cell origin and association with the Epstein-Barr virus (EBV). In the presence of disturbed T-cell function EBV may induce not only prolonged proliferation but also transformation of B-cells. In patients with primary, congenital immunodeficiency the incidence of IALD ranges from 0.7% for patients with X-linked agammaglobulinemia to 12-15% in patients with ataxia telangiectasia. In patients with post-transplant lymphoproliferative disorders (PT-LPD) the incidence varies from 0.5% after bone marrow transplantation to 10% after heart-lung transplantation. PT-LPD are often characterized by a polymorphic cell population. Recent studies identified three categories: plasmacytic hyperplasia, polymorphic lymphoproliferation and B-cell non-Hodgkin's lymphoma (NHL). The plasmacytic hyperplasias are of polyclonal composition, while polymorphic lymphoproliferations and NHL are monoclonal. The precise risk of lymphoma development in HIV infection is not defined, but estimates suggest a prevalence of 3-4%. HIV-related NHLs are divisible by site of manifestation into systemic, primary central nervous system and body-cavity lymphomas, and by pathology into Burkitt's and Burkitt's-like lymphoma, and diffuse large cell lymphoma (DLCL). In about 90% of cases these lymphomas are of monoclonal B-cell composition. Recent experiences suggest a link between therapy with immunosuppressive drugs (methotrexate, azathioprine, cyclophospamide, etc.) and development of IALD, best supported by the increased rate of IALD in patients with rheumatoid arthritis who receive methotrexate therapy. The occurrence of IALD demonstrates the importance of competent immunosurveillance in the development of lymphoid neoplasias, which may have therapeutic relevance too.
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PMID:Immunosurveillance, immunodeficiency and lymphoproliferations. 1178 33