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Study of cancer cell metabolism yields new insights on leukemia
Date:1/17/2013

ed the pathways involved in oxidative phophorylation, with an eye toward finding an Achilles' heel to stop the process. They discovered that an important gene, BCL-2, is elevated and central to leukemia stem cell energy production.

The team also knew that drugs to inhibit BCL-2 are in various stages of development in the pharmaceutical industry; Lagadinou and Jordan found two such compounds and tested them in human leukemia specimens. Their findings showed the drugs preferentially killed inactive and metabolically slower leukemia stem cells.

Leukemia is known for its ability to lie dormant for long periods, despite treatment, but then suddenly begin another assault.

"This treatment shows promise toward a dormant leukemic stem cell subpopulation that is relatively untouched by conventional drugs," Lagadinou said. "It's also important to note that normal cells were not harmed by the compounds, because they can use alternative pathways to generate energy."

Without the toxicity to healthy cells, researchers hope they can target the disease during periods of remission, when mopping up residual leukemia is essential.

Leukemia is a blood cancer with four common types: acute myelogenous leukemia (AML), acute lymphoblastic (ALL), chronic myeloid leukemia (CML), and chronic lymphoblastic (CLL). AML is most common in adults and the most difficult to treat, in part because it affects immature cells. Nearly 50,000 new cases are diagnosed each year, with about half resulting in death.

Investigators have learned during the past decade that many therapies were not designed to kill the root of leukemia, the so called "leukemia stem cells," and therefore never truly eliminate the disease.

In fact, even the most modern cancer treatments were developed under the assumption that all cancer metabolism relies on glycolysis as a fuel source. This makes the URMC study and the discovery that oxidative phosphorylation is the single fuel source for leukemia stem
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Contact: Leslie Orr
Leslie_Orr@urmc.rochester.edu
University of Rochester Medical Center
Source:Eurekalert

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