Project Term
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Cincinnati Children's Hospital Medical Center
Cincinnati, OH
United States
Project Summary
AML is an heterogenous disease with dismal overall survival rates. This is partly due to the presence of leukemic stem cells that drive disease recurrence. LSCs rewire their metabolism to adapt to therapy. Using unbiased lipidomic analysis comparing LSCs to HSPCs, we identified LSCs to be reliant on fatty acid elongase, ELOVL1. By integrating lipidomic, transcriptomics and functional assays, we aim to uncover why AML LSCs rely on ELOVL1 and pave the way for novel therapeutic strategies in AML.
Lay Abstract
Acute myeloid leukemia is an aggressive blood cancer that occurs in both adults and children. Even though present therapies initially target the leukemia cells, in the majority of the patients the disease comes back often resulting in the death of the patient. This is mainly due to a small number of cells that have unique biology allowing them to evade therapy efficiently. These cells are called leukemia stem cells (LSCs). Identifying specific factors that differentiate LSCs from healthy blood cells paves the way for novel therapies that could improve patient outcomes. From our preliminary laboratory work, we identified that LSCs have enhanced levels of molecules named very long chain fatty acids (VLCFA) compared to healthy stem cells. These VLCFAs are made by a helper molecule known as ELOVL1. Testing drugs that target ELOVL1 in the laboratory, we found inhibition of ELOVL1 affected the survival of LSCs. Using advanced technologies, we will stringently test if ELOVL1 can eradicate LSCs in combination with available approved therapies. Eventually opening new therapeutic approaches for AML patients.
Program
Grant Subprogram