Development and Characterization of the Femur Window Chamber Model for Leukemia Research

Acute lymphoblastic leukemia (ALL) is an aggressive disease of the bone marrow (BM) microenvironment. Unfortunately, the difficulty of traditional methodologies to access the BM in vivo has thus far limited our understanding of disease biology. This project therefore advances the femur window chamber (FWC) mouse model as a new tool for intravital imaging and study of the representative BM of long bones. Here, I have optimized the FWC technique for longitudinal leukemia studies and demonstrated minimal disruption to the native BM vasculature and immune landscape from the surgery. I have also determined that ALL progression results in significant BM remodelling, including elevated hypoxia levels, reduced vascular perfusion, increased vessel diameter, and a dynamic cycle of immune cell recruitment then suppression. These findings not only establish important preclinical research methodologies that overcome the limitations of traditional assays, but also characterize significant ALL dynamics that could inform future therapeutic strategies.M.Sc