Modelling Bone Marrow Extracellular Matrix Interactions Reveal CD36-Dependant Vulnerabilities in Acute Myeloid Leukemia

Abstract

Understanding how the bone marrow microenvironment influences metabolic dependencies is crucial for improving therapeutic strategies in acute myeloid leukemia (AML). CD36, a fatty acid transporter associated with lipid uptake and chemoresistance in AML, may be functionally influenced by interactions with the extracellular matrix (ECM). This thesis investigated whether ECM engagement alters CD36-dependent responses in AML. OCI-AML2 cells were cultured on either standard polystyrene (PS) or an ECM-based scaffold and assessed following CD36 inhibition using flow cytometry. Scaffold-cultured cells exhibited reduced viability, fatty acid uptake, and clonogenic capacity under CD36 inhibition compared to PS culture. Primary AML samples were then evaluated to assess patient-specific responses. ECM scaffold culture revealed phenotypic adaptations following CD36 inhibition, including reduced fatty acid uptake and increased CD11b expression for two patient samples, suggestive of enhanced ECM interaction and myeloid differentiation. Overall, these findings demonstrate that ECM interactions modulate CD36-dependent vulnerabilities in AML not evident under standard PS culture conditions.