Large B-cell lymphoma with IRF4 rearrangement is a rare disease that primarily affects children, adolescents and young adults, and generally has a good prognosis. In this disease, fragments of the IRF4 gene’s DNA are broken and rearranged with other chromosomal regions, leading to its overexpression. However, important questions remain about the structure of these rearrangements and whether cases diagnosed in adults truly correspond to the same biological entity.
To answer this question, the research group carried out a comprehensive characterization of the genetic and molecular changes that had occurred in 35 paediatric and young adult patients, and in seven adults over the age of 40.
The results allowed for the identification of new genetic mechanisms involved in these lymphomas, as well as new genes associated with IRF4 rearrangements. “The study demonstrates that IRF4-rearranged lymphomas in children, adolescents and young adults constitute a homogeneous biological entity, with its own molecular mechanisms. In contrast, the cases observed in adults present different genetic characteristics that suggest a distinct biology,” explains Itziar Salaverria, head of the research group and co-leader of the project. “These results allow us to better understand the mechanisms that give rise to these tumours and to advance towards more precise classifications of lymphomas.”
The identified molecular differences are also reflected in the patients’ clinical presentation. Adults more frequently present with advanced disease and the involvement of organs outside the usual sites.
“These findings contribute to enabling more personalized medicine based on the molecular characteristics of the tumour,” highlights Olga Balagué, haematopathologist at the Hospital Clínic de Barcelona and co-leader of the study. “In the future, these results could help us to improve diagnosis and provide a better estimate of prognosis, which could potentially lead to personalized treatment.”
This study was made possible thanks to funding from the Carlos III Health Institute, the Spanish Association Against Cancer (AECC), and the CRIS Cancer Foundation.
Study of reference
Ariadna Colmenero, Leonie Frauenfeld, Sara Mato, Julia Salmerón-Villalobos, Vicente Arredondo-Prats, Joan Enric Ramis-Zaldivar, Anna Montaner, Natalia Castrejon-de-Anta, Blanca Gonzalez-Farre, Noelia Garcia, Jaime Verdu-Amorós, Mara Andres, Maitane Andión, Daniel Azorín, Verónica Celis, Socorro Maria Rodríguez-Pinilla, Carlos Aliste Santos, Eric Hsi, Gabriela Gheorghe, Rachel Angelica Mariani, Kristian T Schafernak, Anna Shestakova, Madhu Menon, Francisco Llamas Gutierrez, Konnie M. Hebeda, Tapan Mahendra Bhavsar, Armando López-Guillermo, Elaine S Jaffe, Leticia Quintanilla-Martinez, Elías Campo, Ferran Nadeu, Olga Balagué, Itziar Salaverria; Genomic Architecture of IRF4 Rearrangements in Children and Adult Large B-cell Lymphomas. Blood Adv 2026; bloodadvances.2026020477. doi: https://doi.org/10.1182/bloodadvances.2026020477
