Recent research has indicated that in the process of generating energy, leukemic cells use a cellular pathway known as fatty acid oxidation, rather than pyruvate oxidation, as had been previously thought.
A team of researchers, at the University of Texas M.D. Anderson Cancer Center, Houston, and the University of Texas Houston Medical School, has now used this knowledge to develop a way to sensitize human leukemic cells to molecules that induce cell death by a process known as apoptosis. They hope that it might be possible to translate this approach to the clinic as a therapeutic strategy to treat leukemias.
The research appears in the Journal of Clinical Investigation.
The team, led by Michael Andreeff and Heinrich Taegtmeyer, found that inhibition of fatty acid oxidation with either etomoxir, a drug that was tested in clinical trials for the treatment of heart disease but never made it to market due to unacceptable toxicities, or ranolazine, a drug approved for the treatment of chronic angina, inhibited human leukemic cell proliferation in vitro. More importantly, etoxomir treatment sensitized human leukemic cells to the death-inducing compound ABT-737 both in vitro and in vivo, in a xenotransplant mouse model of leukemia.
The authors therefore conclude that fatty acid oxidation is essential for human leukemic cell survival and suggest that inhibitors of fatty acid oxidation might provide a new approach to treating leukemias.
- Ismael Samudio, Romain Harmancey, Michael Fiegl, Hagop Kantarjian, Marina Konopleva, Borys Korchin, Kumar Kaluarachchi, William Bornmann, Seshagiri Duvvuri, Heinrich Taegtmeyer and Michael Andreeff. Pharmacologic inhibition of fatty acid oxidation sensitizes human leukemia cells to apoptosis induction. Journal of Clinical Investigation, 2009; DOI: 10.1172/JCI38942
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