| Project Detail |
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. |
