Plasmablastic lymphoma (PBL) is known for its fast progression and poor prognosis, with current treatment options being limited and often ineffective. Through an in-depth molecular analysis of tumour samples, a team led by Dr Tomás Navarro and Dr Míriam Verdú identified that the E2F3 protein, a key regulator of the cell cycle, and survivin, an inhibitor of cell death, are significantly overexpressed in PBL cells, driving unchecked proliferation and resistance to cell death.

Published in the journal Blood Advances, official outlet of the American Society of Hematology, the research represents one of the most comprehensive molecular studies ever conducted on PBL, a disease particularly difficult to diagnose due to its similarity to other types of lymphomas and plasma cell disorders. Dr Navarro’s team used advanced genetic sequencing and molecular profiling techniques to analyse tumour samples from over 50 patients.

The team demonstrated that restoring levels of a tumour-suppressing molecule called miR-150-5p in PBL cells disrupts the effects of E2F3 and survivin, leading to a dramatic reduction in the activity of both molecules. This, in turn, triggers cell death and halts tumour progression. These effects were confirmed in cell cultures, but would need validation from in vivo studies in the future.

Most importantly, the study evaluated the use of two experimental drugs: HLM006474, which inhibits E2F family proteins, and S12, which blocks survivin. The combination of these two agents led to strong anti-cancer effects in PBL preclinical models, reducing cell proliferation and tumour growth.

The implications of this discovery are significant. While PBL is rare, its aggressive nature and poor prognosis make the need for innovative treatment approaches urgent. The identification of E2F3 and survivin as therapeutic vulnerabilities offers a potential path forward for drug development.

As research continues, backed by state-of-the-art genomic tools and in vitro and in vivo models, this breakthrough will pave the way for new diagnostic tools and, ultimately, better outcomes for patients diagnosed with this challenging disease.

This research has been partly funded by the Spanish government and the Josep Carreras Foundation. This text has been produced with the limited assistance of generative AI tools.

Reference article:

Míriam Verdú-Bou, Maria Joao Baptista, Marcelo Lima Ribeiro, Aleix Méndez López, Núria Profitós-Pelejà, Fabian Frontzek, Gaël Roué, José Luís Mate, Mireia Pellicer, Pau Abrisqueta, Josep Castellví, Mariana Beatriz Bastos Oreiro, Javier Menarguez, Miguel Alcoceba, Eva González-Barca, Fina Climent, Antonio Salar, Juan Manuel Sancho, Annette M. Staiger, German Ott, Ioannis Anagnostopoulos, Manel Esteller, Georg Lenz, Gustavo Tapia, José-Tomás Navarro. “The role of miR-150-5p/E2F3/survivin axis in the pathogenesis of plasmablastic lymphoma and its therapeutic potential”. Blood Adv 2025; bloodadvances.2025016180. doi: https://doi.org/10.1182/bloodadvances.2025016180