BCL-6 gene mutations in posttransplantation lymphoproliferative disorders predict response to therapy and clinical outcome
| Autor: | Ethel Cesarman, Amy Chadburn, Yi-Fang Liu, Anna Migliazza, Riccardo Dalla-Favera, Daniel M. Knowles |
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| Rok vydání: | 1998 |
| Předmět: |
Herpesvirus 4
Human Lymphoma B-Cell Immunology DNA Mutational Analysis Biochemistry Proto-Oncogene Mas Postoperative Complications Proto-Oncogene Proteins Proto-Oncogenes Humans Life Tables Polymorphism Single-Stranded Conformational Transplantation Hyperplasia Cell Biology Hematology DNA Neoplasm Herpesviridae Infections Cell Transformation Viral Prognosis Lymphoproliferative Disorders DNA-Binding Proteins Tumor Virus Infections Cell Transformation Neoplastic Treatment Outcome Proto-Oncogene Proteins c-bcl-6 Immunosuppressive Agents Transcription Factors |
| Zdroj: | Blood. 92(7) |
| ISSN: | 0006-4971 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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