The Role of Metabolism in MLL-AF9 Leukemia Initiation

It has been shown that metabolism, which comprises a range of biochemical processes essential for cell functioning, can play a role in the causation of cancer including leukemias. Certain leukemia cells have been shown to have cancer initiating or 'stem cell' potential.  There is little knowledge about the role that metabolism plays in the maintenance of leukemia stem cells.
 
We plan to use a particular model of acute myeloid leukemia called the 'MLL-AF9' model, in which leukemia stem cells have been well defined. We will study the role that metabolic enzymes play in the maintenance of leukemia initiating cells.
 

Gene expression, activity of metabolic enzymes and inhibition of 116 key metabolic enzymes will be studied in MLL-AF9 leukemia initiating cells and in their normal counterparts (from non leukemic mice). A list of enzymes, which have differential activity in leukemia initiating cells versus their normal counterparts, will be derived from these experiments. Enzymes that are overactive in leukemia initiating cells will be down regulated in mice to see if survival of these leukemic mice is improved by this inhibition. We hope that this will translate into a therapeutic strategy for both adults and children with MLL-AF9 acute myeloid leukemia.