title: Molecular histogenesis of posttransplantation lymphoproliferative disorders.
abstract: Posttransplantation lymphoproliferative disorders (PTLDs) represent a serious complication of solid organ transplantation. This study assessed the molecular histogenesis of 52 B-cell monoclonal PTLDs, including 12 polymorphic PTLDs (P-PTLDs), 36 diffuse large B-cell lymphomas (DLBCLs), and 4 Burkitt/Burkitt-like lymphomas (BL/BLLs). Somatic hypermutation (SHM) of immunoglobulin variable (IgV) genes documented that most monoclonal B-cell PTLDs (75% P-PTLDs, 91.3% DLBCLs, 100% BL/BLLs) derive from germinal center (GC)-experienced B cells. B-cell lymphoma 6 (BCL6) mutations occurred in 25% P-PTLDs, 60.6% DLBCLs, and 75.0% BL/BLLs. A first histogenetic category of PTLDs (31.2% DLBCLs) express the BCL6+/multiple myeloma oncogene-1 protein (MUM1-/+)/CD138- profile and mimic B cells experiencing the GC reaction, as also suggested by ongoing SHM in a fraction of these cases. A second subset of PTLDs (66.7% P-PTLDs and 31.2% DLBCLs) display the BCL6-/MUM1+/CD138- phenotype and mimic B cells that have concluded the GC reaction. A third histogenetic category of PTLDs (25.0% P-PTLDs and 31.2% DLBCLs) shows the BCL6-/MUM1+/CD138+ profile, consistent with preterminally differentiated post-GC B cells. Crippling mutations of IgV heavy chain (IgVH) and/or IgV light chain (IgVL) genes, leading to sterile rearrangements and normally preventing cell survival, occur in 4 DLBCLs and 1 BL/BLL that may have been rescued from apoptosis through expression of Epstein-Barr virus (EBV)-encoded latent membrane protein 1 (LMP1). Overall, the histogenetic diversity of monoclonal B-cell PTLDs may help define biologically homogeneous categories of the disease.
authors.affiliation: Hematology Unit, Department of Medical Sciences & Interdisciplinary Research Center on Autoimmune Diseases, Amedeo Avogadro University of Eastern Piedmont, Via Solaroli 17, 28100 Novara, Italy.
authors.forename: Daniela
authors.initials: D
authors.lastname: Capello
authors.forename: Michaela
authors.initials: M
authors.lastname: Cerri
authors.forename: Giuliana
authors.initials: G
authors.lastname: Muti
authors.forename: Eva
authors.initials: E
authors.lastname: Berra
authors.forename: Pierluigi
authors.initials: P
authors.lastname: Oreste
authors.forename: Clara
authors.initials: C
authors.lastname: Deambrogi
authors.forename: Davide
authors.initials: D
authors.lastname: Rossi
authors.forename: Giampietro
authors.initials: G
authors.lastname: Dotti
authors.forename: Annarita
authors.initials: A
authors.lastname: Conconi
authors.forename: Mario
authors.initials: M
authors.lastname: Viganò
authors.forename: Umberto
authors.initials: U
authors.lastname: Magrini
authors.forename: Giovanbattista
authors.initials: G
authors.lastname: Ippoliti
authors.forename: Enrica
authors.initials: E
authors.lastname: Morra
authors.forename: Annunziata
authors.initials: A
authors.lastname: Gloghini
authors.forename: Alessandro
authors.initials: A
authors.lastname: Rambaldi
authors.forename: Marco
authors.initials: M
authors.lastname: Paulli
authors.forename: Antonino
authors.initials: A
authors.lastname: Carbone
authors.forename: Gianluca
authors.initials: G
authors.lastname: Gaidano
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D001402:B-Lymphocytes / Q000473:pathology; D001483:Base Sequence; D002648:Child; D002675:Child, Preschool; D005260:Female; D015321:Gene Rearrangement; D005803:Genes, Immunoglobulin; D004854:Herpesvirus 4, Human; D006801:Humans; D016130:Immunophenotyping; D007223:Infant; D008232:Lymphoproliferative Disorders / Q000209:etiology* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D016377:Organ Transplantation / Q000009:adverse effects*; D012189:Retrospective Studies; D027041:Somatic Hypermutation, Immunoglobulin; D014763:Viral Matrix Proteins / Q000502:physiology
chemical_list: C037662:EBV-associated membrane antigen, Epstein-Barr virus; D014763:Viral Matrix Proteins