Project description
Understanding the role of RAS-mutated subclones in leukaemia progression
High hyperdiploid acute lymphoblastic leukaemia (HeH ALL) features RAS-mutant subclones that may drive disease progression. While this common childhood ALL subtype has a favourable prognosis, it is prone to relapse. HeH ALL is marked by multiple chromosome gains and RAS mutations, which could be potential therapeutic targets. Supported by the Marie Skłodowska-Curie Actions programme, the RasWayToALL project will analyse the molecular profiles of HeH ALL clones using single-cell multi-omic technologies. It will focus on RAS subclonal alterations and assess their in vivo impact using patient-derived xenograft (PDX) models and RAS-targeting drugs. It aims to identify expression patterns in RAS-mutated subclones that clarify their role in leukaemia progression and their potential as targets for personalised therapy.
Objective
In high hyperdiploid acute lymphoblastic leukemia (HeH ALL), RAS-mutant subclones may represent the “RASwaytoALL”, a critical evolutionary route that fuels leukemic progression. HeH ALL is the most common subtype of childhood ALL. Despite its generally favorable prognosis, it remains a major cause of relapse. Genetically, this leukemia is characterized by the gain of multiple chromosomes (51–68 in total) and an intriguing genetic mystery: single-cell DNA sequencing performed by the host laboratory revealed that all studied HeH ALL patients harbor subclonal mutations in RAS pathway genes, arising from the hyperdiploid clone. The biological and clinical significance of these RAS-mutant subclones remains unknown. I hypothesize that RAS-mutant subclones actively contribute to HeH ALL progression and may represent a therapeutically targetable vulnerability. The project has two main objectives: (i) characterize the molecular profile of HeH ALL clones using single-cell multi-omic technologies, focusing on the function of RAS subclonal alterations (ii) assess the functional impact of RAS subclonal alterations in vivo by establishing patient-derived-xenograft (PDX) models and using RAS targeting drugs. I expect to identify expression patterns in RAS-mutated subclones that explain their role in leukemia progression and demonstrate their potential as targets for personalized therapy. The proposal builds on my expertise in omics data analysis, ALL clinical and genetics, and PDX models, along with the pioneering work of the host lab in single-cell technologies, in vivo modelling, and mechanistic studies of ALL. The host institution offers access to cutting-edge facilities and strong collaborative networks. This project will enhance my experimental skills, consolidating my profile as an independent researcher at the interface of genomics, cancer biology, and translational hematology.
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 genetics DNA
- natural sciences biological sciences genetics mutation
- medical and health sciences clinical medicine hematology
- medical and health sciences clinical medicine oncology leukemia
- natural sciences biological sciences genetics chromosomes
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Project’s keywords as indicated by the project coordinator. Not to be confused with the EuroSciVoc taxonomy (Fields of science)
Project’s keywords as indicated by the project coordinator. Not to be confused with the EuroSciVoc taxonomy (Fields of science)
Programme(s)
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Multi-annual funding programmes that define the EU’s priorities for research and innovation.
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HORIZON.1.2 - Marie Skłodowska-Curie Actions (MSCA)
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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-TMA-MSCA-PF-EF - HORIZON TMA MSCA Postdoctoral Fellowships - European Fellowships
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(opens in new window) HORIZON-MSCA-2025-PF
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9052 ZWIJNAARDE - GENT
Belgium
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