BCL-6 gene mutations in posttransplantation lymphoproliferative disorders predict response to therapy and clinical outcome
BCL-6 gene mutations in posttransplantation lymphoproliferative disorders predict response to therapy and clinical outcome
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DOI：
10.1182/blood.v92.7.2294.2294_2294_2302
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发表时间：
1998-10-01
期刊：
影响因子：
20.3
通讯作者：
Knowles, DM
中科院分区：
文献类型：
--
作者：
Cesarman, E;Chadburn, A;Knowles, DM
移植后淋巴组织增生性疾病（PT-LPDs）是一组异质性EB病毒相关的淋巴组织增生，出现在免疫抑制移植受者。这些病变中的一些在免疫抑制剂治疗减少后消退，而一些尽管积极治疗仍会进展。形态学、免疫表型和免疫基因型标准在预测临床结果方面并不实用。虽然在一些PT-LPD中发现的癌基因和/或肿瘤抑制基因的结构改变与不良的临床结局相关，但这些改变的存在并不是减少免疫抑制后病变消退的一贯有用的预测因子。我们使用单链构象多态性和序列分析检测了来自36例实体器官移植受者的57个PT-LPD病变中BCL-6原癌基因突变的存在，随后与33例患者的组织病理学分类和临床结局进行相关性分析。BCL-6基因突变在44%的标本和44%的患者中被发现;在浆细胞增生的病例中没有发现。然而，突变存在于43%的多态性病变和90%的PT-LPD诊断为非霍奇金淋巴瘤或多发性骨髓瘤。BCL-6基因突变可预测PT-LPDs的生存期缩短，对免疫抑制和/或手术切除的抵抗力降低。我们的研究结果表明，BCL-6基因结构是将PT-LPDs分为增生和恶性淋巴瘤的生物学类别的可靠指标，其中只有前者可以在免疫重建方面消退。BCL-6基因突变的存在可能是一个有用的临床标志物，以确定是否减少免疫抑制应尝试或更积极的治疗应制定。(C)1998年美国血液学会。
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. (C) 1998 by The American Society of Hematology.