Abstract 67: Deciphering the mechanisms underlying the pathophysiology and chemotherapy resistance in acute myeloid leukemia using intravital imaging and humanized NSGW41IL7 mouse

Introduction: Acute Myeloid Leukemia (AML) is an aggressive & highly heterogeneous malignancy that originates within the bone marrow (BM). A major challenge in treating AML is its resistance to therapy & high relapse rates, driven in part by changes AML induces in the BM microenvironment, promoting immune suppression & creating hypoxic conditions. However, the mechanisms behind therapeutic resistance in AML patients in the presence of hypoxic BM niche, are poorly understood.Innovation & Clinical Impact: To address this knowledge gap, our study employs two pioneering methods: a humanized NSGW41IL7 mouse model engrafted with human AML cells & the femur window chamber (FWC) technique, enabling unprecedented real-time visualization of AML dynamics within BM. Using advanced intravital imaging, we are the first to observe the intricate, continuous interactions between AML cells & immune components, such as human gamma delta T cells, within the BM microenvironment. Furthermore, we are interested in using our new approach to investigate how standard chemotherapies impact AML cell survival & immune responses under hypoxic conditions over time. Ultimately, our findings will provide new insights into treatment resistance mechanisms & pave the way for innovative therapeutic strategies targeting the BM microenvironment, improving outcomes for AML patients. Citation Format: Raheleh Niavarani, Xi Lei, Michael Edson, Emily Chen, Shirley Wang, Ralph DaCosta. Deciphering the mechanisms underlying the pathophysiology and chemotherapy resistance in acute myeloid leukemia using intravital imaging and humanized NSGW41IL7 mouse [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 67.