title: Epstein-Barr virus infection and altered control of apoptotic pathways in posttransplant lymphoproliferative disorders.
abstract: Posttransplant lymphoproliferative disorders (PTLD) represent a spectrum of lymphoid diseases complicating the clinical course of transplant recipients. Most PTLD are Epstein-Barr virus (EBV) associated with viral latency type III. Several in vitro studies have revealed an interaction between EBV latency proteins and molecules of the apoptosis pathway. Data on human PTLD regarding an association between Bcl-2 family proteins and EBV are scarce. We analyzed 60 primary PTLD for expression of 8 anti- (Bcl-2, Bcl-XL, and Mcl-1) and proapoptotic proteins (Bak and Bax), the so-called BH3-only proteins (Bad, Bid, Bim, and Puma), as well as the apoptosis effector cleaved PARP by immunohistochemistry. Bim and cleaved PARP were both significantly (p = 0.001 and p = 5.251e-6) downregulated in EBV-positive compared to EBV-negative PTLD [Bim: 6/40 (15%), cleaved PARP: 10/43 (23%), vs. Bim: 13/16 (81%), cleaved PARP: 12/17 (71%)]. Additionally, we observed a tendency toward increased Bcl-2 protein expression (p = 0.24) in EBV-positive PTLD. Hence, we provide evidence of a distinct regulation of Bcl-2 family proteins in EBV-positive versus negative PTLD. The low-expression pattern of the proapoptotic proteins Bim and cleaved PARP together with the high-expression pattern of the antiapoptotic protein Bcl-2 by trend in EBV-positive tumor cells suggests disruption of the apoptotic pathway by EBV in PTLD, promoting survival signals in the host cells.
authors.affiliation: Service d'Anatomie et Cytologie Pathologiques, Hôpital Paul-Brousse, Hôpital Bicêtre, AP-HP, Université Paris-Sud, France.
authors.forename: Maria-Rosa
authors.initials: MR
authors.lastname: Ghigna
authors.forename: Tanja
authors.initials: T
authors.lastname: Reineke
authors.forename: Patricia
authors.initials: P
authors.lastname: Rincé
authors.forename: Peter
authors.initials: P
authors.lastname: Schüffler
authors.forename: Bouchra
authors.initials: B
authors.lastname: El Mchichi
authors.forename: Monique
authors.initials: M
authors.lastname: Fabre
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Jacquemin
authors.forename: Antoine
authors.initials: A
authors.lastname: Durrbach
authors.forename: Didier
authors.initials: D
authors.lastname: Samuel
authors.forename: Irène
authors.initials: I
authors.lastname: Joab
authors.forename: Catherine
authors.initials: C
authors.lastname: Guettier
authors.forename: Marco
authors.initials: M
authors.lastname: Lucioni
authors.forename: Marco
authors.initials: M
authors.lastname: Paulli
authors.forename: Marianne
authors.initials: M
authors.lastname: Tinguely
authors.forename: Martine
authors.initials: M
authors.lastname: Raphael
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D017209:Apoptosis; D051017:Apoptosis Regulatory Proteins / Q000378:metabolism*; D015415:Biomarkers / Q000378:metabolism; D002648:Child; D002675:Child, Preschool; D020031:Epstein-Barr Virus Infections / Q000150:complications / Q000378:metabolism / Q000473:pathology*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D004854:Herpesvirus 4, Human / Q000502:physiology*; D006801:Humans; D007150:Immunohistochemistry; D007223:Infant; D008232:Lymphoproliferative Disorders / Q000209:etiology / Q000378:metabolism / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D016377:Organ Transplantation / Q000009:adverse effects; D011183:Postoperative Complications; D017735:Virus Latency; D055815:Young Adult
chemical_list: D051017:Apoptosis Regulatory Proteins; D015415:Biomarkers