Molecular histogenesis of posttransplantation lymphoproliferative disorders

Daniela Capello, Michaela Cerri, Giuliana Muti, Eva Berra, Pierluigi Oreste, Clara Deambrogi, Davide Rossi, Giampietro Dotti, Annarita Conconi, Mario Viganò, Umberto Magrini, Giovanbattista Ippoliti, Enrica Morra, Annunziata Gloghini, Alessandro Rambaldi, Marco Paulli, Antonino Carbone, Gianluca Gaidano

Risultato della ricerca: Contributo su rivistaArticolo in rivistapeer review

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 (IgV H) 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.

Lingua originaleInglese
pagine (da-a)3775-3785
Numero di pagine11
RivistaBlood
Volume102
Numero di pubblicazione10
DOI
Stato di pubblicazionePubblicato - 15 nov 2003

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