BCL-6 gene mutations in posttransplantation lymphoproliferative disorders predict response to therapy and clinical outcome.

TitleBCL-6 gene mutations in posttransplantation lymphoproliferative disorders predict response to therapy and clinical outcome.
Publication TypeJournal Article
Year of Publication1998
AuthorsCesarman E, Chadburn A, Liu YF, Migliazza A, Dalla-Favera R, Knowles DM
Date Published1998 Oct 01
KeywordsCell Transformation, Neoplastic, Cell Transformation, Viral, DNA Mutational Analysis, DNA, Neoplasm, DNA-Binding Proteins, Herpesviridae Infections, Herpesvirus 4, Human, Humans, Hyperplasia, Immunosuppressive Agents, Life Tables, Lymphoma, B-Cell, Lymphoproliferative Disorders, Polymorphism, Single-Stranded Conformational, Postoperative Complications, Prognosis, Proto-Oncogene Proteins, Proto-Oncogene Proteins c-bcl-6, Proto-Oncogenes, Transcription Factors, Transplantation, Treatment Outcome, Tumor Virus Infections

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.

Alternate JournalBlood
PubMed ID9746767
Grant ListCA68939 / CA / NCI NIH HHS / United States
CA73531 / CA / NCI NIH HHS / United States
Related Faculty: 
Amy Chadburn, M.D. Ethel Cesarman, M.D., Ph.D.

Pathology & Laboratory Medicine 1300 York Avenue New York, NY 10065 Phone: (212) 746-6464
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