Concerted efforts to define the HSC bone marrow niche have pointed towards a functional role of many different cell types such as the osteoblasts, mesenchymal stromal cells, endothelial cells and the perivascular CAR cells. The significant interest in defining the microenvironment of HSCs has sparked research on defining the niche of hematological disorders that arise from these cells, such as Myelodysplastic Syndromes (MDS) and AML (Acute Myeloid Leukemia). In this context, our earlier work has shown that CD98-mediated adhesive interactions of leukemic stem cells with the endothelium are essential in sustaining these aggressive AML stem cell populations (Bajaj et al., Cancer Cell, 2016). Since the bone marrow microenvironment is known to be altered in MDS, and microenvironmental support is particularly important for MDS cell survival, it is likely that the leukemia-niche interactions that are important for AML growth also play a role in MDS progression. We are thus interested in defining the molecular effectors of these microenvironmental interactions and establishing their role in MDS progression using a combination of human MDS cells, genetic murine models and high-resolution in vivo imaging.