Project description
Transforming bone marrow to fight leukaemia
Acute Myeloid Leukemia (AML) is a devastating blood cancer marked by the uncontrolled growth of myeloid cells that overtake the bone marrow, impairing its vital functions. Prognosis remains dire, particularly for older adults, with fewer than 10 % of patients over 60 surviving beyond five years. Emerging research highlights the role of the bone marrow (BM) microenvironment in shielding leukaemic cells from chemotherapy and fostering relapse. Among BM components, bone marrow adipose tissue (BMAT) plays a key, yet poorly understood, role. Supported by the Marie Skłodowska-Curie Actions programme, the SMART-AML project leverages advanced bioprinting to create a 3D humanised BM model to study BMAT’s role in AML progression. By manipulating BMAT, the project aims to improve chemotherapy effectiveness, thereby reducing relapse rates.
Objective
Acute Myeloid Leukemia (AML) is an aggressive hematologic malignancy characterized by the uncontrolled proliferation of myeloid cells, which hijack the bone marrow (BM) and compromise its physiological functions. AML prognosis remains poor, with <10% of patients above 60 years old surviving after 5-years.
Recent discoveries have revealed the key role of BM microenvironment in harboring and protecting leukemic stem cells from chemotherapy, contributing to AML relapse. Therefore, targeting the hijacked BM niche and transforming it into a “tumor-inhospitable” microenvironment represents a promising therapeutic strategy. In adults, bone marrow adipose tissue (BMAT) is the predominant component of the BM microenvironment, making it an appealing target. However, the role of BMAT in AML development, drug resistance and survival is still controversial.
With SMART-AML, I aim at identifying AML cells-related changes within the BMAT/BM microenvironment, to introduce BMAT manipulation as therapeutic strategy to sensitize leukemic cells to chemotherapy. To achieve this goal, I will exploit state-of-the-art bioprinting technologies to engineer a perfusable, humanized bone/BMAT 3D biomimetic microenvironment. Patient-derived AML cells will be cultured within the engineered platform to characterize the AML-induced BMAT changes in a controlled environment, with limited variables. Finally, BMAT will be manipulated (i.e. expanded or reduced), to determine the potential of this therapeutic approach on enhancing the efficacy of chemotherapy on leukemic stem cells and reducing the chance of relapse.
This project will prepare me to become a tenured scholar, strengthening my academic profile and enabling me to establish myself as an independent principal investigator with a research line on advanced bone disease modeling. It will also create opportunities to perform cutting-edge research at the intersection between tissue engineering and cancer research.
Fields of science (EuroSciVoc)
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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)
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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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Call for proposal
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(opens in new window) HORIZON-MSCA-2023-PF-01
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3584 CX Utrecht
Netherlands
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