Details

Autor(en) / Beteiligte

• Salmerón-Villalobos, Julia
• Castrejón-de-Anta, Natalia
• Guerra-García, Pilar
• Ramis-Zaldivar, Joan Enric
• López-Guerra, Mónica
• Mato, Sara
• Colomer, Dolors
• Diaz-Crespo, Francisco
• Menarguez, Javier
• Garrido-Pontnou, Marta
• Andrés, Mara
• García-Fernández, Eugenia
• Llavador, Margarita
• Frigola, Gerard
• García, Noelia
• González-Farré, Blanca
• Martín-Guerrero, Idoia
• Garrido-Colino, Carmen
• Astigarraga, Itziar
• Fernández, Alba
• Verdú-Amorós, Jaime
• González-Muñíz, Soledad
• González, Berta
• Celis, Verónica
• Campo, Elías
• Balagué, Olga
• Salaverria, Itziar

Titel

Decoding the molecular heterogeneity of pediatric monomorphic post–solid organ transplant lymphoproliferative disorders

Ist Teil von

• Blood, 2023-08, Vol.142 (5), p.434-445

Ort / Verlag

United States: Elsevier Inc

Erscheinungsjahr

2023

Quelle

Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals

Beschreibungen/Notizen

• •The mutational profile of pediatric PTLD-BL resembles immunocompetent EBV-positive BL, suggesting the need of intensive therapy.•Pediatric PTLD-DLBCL is genetically less complex than the adult PTLD-DLBCL and pediatric immunocompetent DLBCL. [Display omitted] Posttransplant lymphoproliferative disorders (PTLDs) represent a broad spectrum of lymphoid proliferations, frequently associated with Epstein-Barr virus (EBV) infection. The molecular profile of pediatric monomorphic PTLDs (mPTLDs) has not been elucidated, and it is unknown whether they display similar genetic features as their counterpart in adult and immunocompetent (IMC) pediatric patients. In this study, we investigated 31 cases of pediatric mPTLD after solid organ transplantation, including 24 diffuse large B-cell lymphomas (DLBCLs), mostly classified as activated B cell, and 7 cases of Burkitt lymphoma (BL), 93% of which were EBV positive. We performed an integrated molecular approach, including fluorescence in situ hybridization, targeted gene sequencing, and copy number (CN) arrays. Overall, PTLD-BL carried mutations in MYC, ID3, DDX3X, ARID1A, or CCND3 resembling IMC-BL, higher mutational burden than PTLD-DLBCL, and lesser CN alterations than IMC-BL. PTLD-DLBCL showed a very heterogeneous genomic profile with fewer mutations and CN alterations than IMC-DLBCL. Epigenetic modifiers and genes of the Notch pathway were the most recurrently mutated in PTLD-DLBCL (both 28%). Mutations in cell cycle and Notch pathways correlated with a worse outcome. All 7 patients with PTLD-BL were alive after treatment with pediatric B-cell non-Hodgkin lymphoma protocols, whereas 54% of patients with DLBCL were cured with immunosuppression reduction, rituximab, and/or low-dose chemotherapy. These findings highlight the low complexity of pediatric PTLD-DLBCL, their good response to low-intensity treatment, and the shared pathogenesis between PTLD-BL and EBV-positive IMC-BL. We also suggest new potential parameters that could help in the diagnosis and the design of better therapeutic strategies for these patients. Salmerón-Villalobos and colleagues examined the molecular landscape of pediatric monomorphic posttransplant lymphoproliferative disorders in 31 solid-transplant recipients. This disorder can present as diffuse large B-cell lymphoma (DLBCL) or as Burkitt lymphoma (BL), which is usually positive for Epstein-Barr virus (EBV). Patients with DLBCL are heterogeneous and distinct from de novo DLBCL and frequently respond to a reduction of immunosuppression, rituximab, or low-dose chemotherapy. By contrast, BL resembles de novo EBV+ BL and is best treated with combined therapy used for de novo BL.