Fuertes, TeresaÁlvarez Corrales, EmigdioGómez Escolar, CarmenUbieto Capella, PatriciaSerrano Navarro, ÁlvaroDe Molina, AntonioMéndez, JuanRamiro, AlmudenaGarcía-Yébenes Mena, Virginia PilarGarcía-Yébes Mena, Virginia Pilar2023-11-212023-11-212023¡Fuertes, T., Álvarez-Corrales, E., Gómez-Escolar, C. et al. miR-28-based combination therapy impairs aggressive B cell lymphoma growth by rewiring DNA replication. Cell Death Dis 14, 687 (2023). https://doi.org/10.1038/s41419-023-06178-02041-488910.1038/s41419-023-06178-0https://hdl.handle.net/20.500.14352/88881Diffuse large B cell lymphoma (DLBCL) is the most common aggressive B cell lymphoma and accounts for nearly 40% of cases of B cell non-Hodgkin lymphoma. DLBCL is generally treated with R-CHOP chemotherapy, but many patients do not respond or relapse after treatment. Here, we analyzed the therapeutic potential of the tumor suppressor microRNA-28 (miR-28) for DLBCL, alone and in combination with the Bruton’s tyrosine kinase inhibitor ibrutinib. Combination therapy with miR-28 plus ibrutinib potentiated the anti-tumor effects of monotherapy with either agent by inducing a specific transcriptional cell-cycle arrest program that impairs DNA replication. The molecular actions of miR-28 and ibrutinib synergistically impair DNA replication by simultaneous inhibition of origin activation and fork progression. Moreover, we found that downregulation of the miR-28-plus-ibrutinib gene signature correlates with better survival of ABC-DLBCL patients. These results provide evidence for the effectiveness of a new miRNA-based ibrutinib combination therapy for DLBCL and unveil the miR-28-plus-ibrutinib gene signature as a new predictor of outcome in ABC-DLBCL patients.engAttribution 4.0 Internationalhttp://creativecommons.org/licenses/by/4.0/journal articlehttps://doi.org/10.1038/s41419-023-06178-0open access616-006.4LinfomaMicroRNATerapiaCiencias Biomédicas24 Ciencias de la Vida