Poorly differentiated aggressive myeloid diseases are often resistant to standard therapy and associated with significantly poor survival in both children and adults. There is thus a significant need for a better understanding of the mechanisms that drive disease progression and for finding novel therapeutic targets. While intrinsic signals that drive myeloid cancer progression are well described, little is known about how interactions with the surrounding microenvironment can control leukemic growth and propagation. The primary goal of the Bajaj lab is to define the role of cancer stem cell interactions with their microenvironment in disease progression. To address these questions, we use genetic mouse models of human disease and primary human patient samples, CRISPR screening, as well as real time imaging techniques. In the long term, these studies will not only add to our understanding of the niche in the development and progression of hematological malignancies, but may also contribute to the design of novel therapies.