Project description
Chronic lymphocytic leukaemia’s life histories for improved treatments
Cancer history is vital for improving prevention and treatment. Studying the normal cellular counterpart (NCC), the cell of origin (COO), clonal evolution, and tumour microenvironment interactions is crucial. In chronic lymphocytic leukaemia (CLL) and Richter transformation (RT), many aspects of tumour development are still unclear. The ERC-funded CLL-STORY project will reconstruct the life histories of patients with CLL to improve clinical outcomes. The project will create a multi-omic atlas of normal B cells, clarifying the nature of NCCs and the role of (epi)genetic factors in promoting CLL. It will also investigate the COO of CLL and its lifelong trajectories, helping to identify the disease’s origins, growth patterns, and mechanisms of resistance to immune therapies.
Objective
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.
Fields of science (EuroSciVoc)
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: The European Science Vocabulary.
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: The European Science Vocabulary.
- natural sciences biological sciences biological morphology comparative morphology
- humanities history and archaeology history
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Project’s keywords as indicated by the project coordinator. Not to be confused with the EuroSciVoc taxonomy (Fields of science)
Programme(s)
Multi-annual funding programmes that define the EU’s priorities for research and innovation.
Multi-annual funding programmes that define the EU’s priorities for research and innovation.
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HORIZON.1.1 - European Research Council (ERC)
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Calls for proposals are divided into topics. A topic defines a specific subject or area for which applicants can submit proposals. The description of a topic comprises its specific scope and the expected impact of the funded project.
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Funding scheme (or “Type of Action”) inside a programme with common features. It specifies: the scope of what is funded; the reimbursement rate; specific evaluation criteria to qualify for funding; and the use of simplified forms of costs like lump sums.
HORIZON-ERC - HORIZON ERC Grants
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Call for proposal
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(opens in new window) ERC-2025-STG
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08036 Barcelona
Spain
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