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Temple scientists target DNA repair to eradicate leukemia stem cells
Date:12/9/2012

(Philadelphia, PA) Despite treatment with imatinib, a successful drug that targets chronic myeloid leukemia (CML), a deadly type of cancer, some patients may continue to be at risk for relapse because a tiny pool of stem cells is resistant to treatment and may even accumulate additional genetic aberrations, eventually leading to disease progression and relapse. These leukemia stem cells are full of genetic errors, loaded with potentially lethal breaks in DNA, and are in a state of constant self-repair.

Now, scientists at Temple University School of Medicine may have figured out a way to corral this stem cell activity and stunt further cancer development. In a series of experiments in mice with cancer and in cancer cells, they have shown that they can block the process by which leukemia stem cells repair themselves by targeting a particular protein, RAD52, which the cells depend on to fix genetic mistakes. The findings may lead to a new strategy to help overcome drug resistance that hinges on cancer stem cells gone awry.

The researchers report their findings December 9 in a plenary scientific session at the 54th American Society of Hematology Annual Meeting and Exposition in Atlanta.

"We would like to eradicate the leukemia stem cells and cure patients with CML," said senior author Tomasz Skorski, MD, PhD, Professor of Microbiology and Immunology at Temple University School of Medicine. "We took advantage of the fact that remaining leukemia stem cells accumulate lots of lethal DNA lesions, but they don't die because they can repair them very efficiently. We attacked the DNA repair pathway in a way that is not going to harm normal cells, which have a different repair mechanism than leukemia cells."

Targeting Key Repair Protein

The trick, the researchers say, lies in a process called "synthetic lethality," which is defined as a genetic combination of mutations in two or more genes that leads to cell death, wher
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Contact: Steven Benowitz
steven.benowitz@tuhs.temple.edu
215-707-4784
Temple University Health System
Source:Eurekalert

Page: 1 2 3

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