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Blood, Vol. 92 No. 7 (October 1), 1998:
pp. 2294-2302
BCL-6 Gene Mutations in Posttransplantation Lymphoproliferative
Disorders Predict Response to Therapy and Clinical Outcome
Ethel Cesarman,
Amy Chadburn,
Yi-Fang Liu,
Anna Migliazza,
Riccardo Dalla-Favera, and
Daniel M. Knowles
From the Department of Pathology, The New York Hospital-Cornell
Medical Center; and the Department of Pathology and the Department of
Genetics and Development, College of Physicians and Surgeons, Columbia
University, New York, NY.
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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