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Financement de l’UE (1 827 291 €) : Déchiffrer les histoires de vie de la leucémie lymphocytaire chronique pour améliorer les résultats cliniques Hor01/12/2025 Programme de recherche et d'innovation de l'UE « Horizon »
Texte
Déchiffrer les histoires de vie de la leucémie lymphocytaire chronique pour améliorer les résultats cliniques
A holistic view of the history of cancer is not only essential to better understand its pathogenesis, but also has a clear impact by improving future prevention schemes, personalized management strategies, and treatment options. Importantly, the roadmap of a tumor is incomplete without knowing the molecular composition of its normal cellular counterpart (NCC), cell of origin (COO), clonal trajectories, and interactions with the tumor microenvironment influencing disease progression and response to therapy. In chronic lymphocytic leukemia (CLL), the most common adult leukemia in Western countries, and Richter transformation (RT), its aggressive progression, these fundamental aspects remain largely unknown. In this project, named CLL-STORY, I aim to fully reconstruct the life histories of CLL to improve clinical outcome. To that end, using novel methodological breakthroughs and functional readouts, I will (1) generate a detailed multi-omic atlas of normal B cells to properly delineate the NCCs of CLL and their precise nature, allowing me to clarify the role of (epi)genetic drivers in CLL promotion, (2) characterize the COO of CLL and its lifelong clonal trajectories to resolve the disease origin and growth patterns dictating the different clinical courses, with the ultimate aim to control early disease precursors and anticipate disease evolution, and (3) determine the mechanisms of resistance to immune-based therapies, as well as intrinsic and extrinsic features influencing their anti-tumor efficacy, to aid the development of predictive models and improvement of current treatments, which shall improve clinical outcome. In summary, CLL-STORY explores uncharted territories unraveling clonal mosaicism, early cancer development, tumor phylogenies along human lifespan, and mechanisms of treatment failure, hence providing key knowledge, tools, and enhanced treatment options with clear implications reaching beyond CLL, that will bring the entire cancer biology field forward.
| Fundacio de Recerca Clinic Barcelona-Institut D Investigacions Biomediques August Pi i Sunyer | 1 827 291 € |
| Hospital Clinic de Barcelona | 0,00 € |
https://cordis.europa.eu/project/id/101222226
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