Grant: Project Grant

One reason that blood cancers such as acute myeloid leukemia (AML) are so difficult to cure is that current therapies are targeted against the bulk of the blood cancer cells but somehow miss the leukemia stem cells (LSCs) that contribute significantly to disease relapse after treatment. These LSCs can evade therapy and give rise to disease relapse because they are stuck in an aberrant stem cell state that continues to fuel new rounds of disease. This project deals with the transcription factors of the ZEB and SNAI families and how when their expression is increased in AML they can alter epigenetic control factors that lead to LSC disease causing state. Here we will show that if you decrease ZEB and SNAI or get rid of them completely in blood cancer stem cells then the epigenetic factors that they interact with will no longer drive the LSC state and the cancer cells will become easier to target. We will use mouse models of AML and human AML cell lines and primary patient cells to identify new ways of eliminating LSCs during this project. This project will identify new targets and approaches to treat blood cancers but the findings may also be useful for other forms of solid tumour cancers that are also driven by cancer stem cells.