An important objective of the POl application is to define the contribution of altered sphingolipid metabolism in Acute Myeloid Leukemia (AML). Through the multiple Projects, the roles of specific sphingolipids and sphingolipid enzymes in AML and the efficacy of therapeutically targeting sphingolipid metabolism for AML will be defined. In order to achieve these objectives the Targeted Sphing"omics" Core will provide critical information to the Projects through two objectives;1) The Core will quantify changes in the sphingolipidome (lipids and proteins), identifying new therapeutic targets for AML, and testing the efficacy of sphingolipid-based therapeutics and 2) the Core will provide standardized measurements of sphingolipids and their metabolizing enzymes for all four Projects. These objectives will create new hypotheses into the roles of sphingolipids in AML and serves to assist the Projects in testing their specific hypotheses. Taken together, this will lead to an understanding of the contributions of, and therapeutic efficacy of, targeting sphingolipid metabolism.
Acute Myeloid Leukemia (AML) is the most common acute leukemia affecting adults. The complexity of AML is attributed to multiple subtypes based on cyto- and molecular-genetics. This Core serves a role in hypothesis generation for the Projects by seeking to understand alterations in sphingolipid and glycosphingolipid metabolism within different subsets of patients with AML and hypothesis testing by providing standardized measurements of the sphingolipid pathways. The outcome of these studies will help validate and define new sphingolipid-based therapeutic targets for AML.