Sensitizing Leukemic Cells To Death-Inducing Compounds

Main Category: Lymphoma / Leukemia / Myeloma
Also Included In: Clinical Trials / Drug Trials
Article Date: 22 Dec 2009 - 2:00 PST

email to a friend   printer friendly   opinions  

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 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.

TITLE: Pharmacologic inhibition of fatty acid oxidation sensitizes human leukemia cells to apoptosis induction

AUTHOR: Michael Andreeff, University of Texas M.D. Anderson Cancer Center, Houston, Texas, USA.

Journal of Clinical Investigation, December 21, 2009

Source: Karen Honey
Journal of Clinical Investigation

• Additional
• References
• Citations