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UCSF team discovers key to fighting drug-resistant leukemia
Date:5/18/2011

enjoy complete remission and are able to live cancer-free, cured of the leukemia.

Still a large number of children are not cured and ultimately succumb to the disease. In those cases, some of the cancer cells resist the therapy and survive quietly in the body. When the cancer reemerges, it is no longer sensitive to the drugs.

In their new report, Mschen and his colleagues show that the key to this resistance is the protein BCL6, offering the first evidence of how the cancer cells managed to survive.

"It is something like an emergency mechanism whereby tumor cells try to evade drug-treatment," Mschen said.

ONE AMONG 22,000 GENES

The work started four years ago when Mschen wanted to figure out what happens to cancer cells during cancer treatments. He and his colleagues exposed leukemia cells in the petri dish to drugs and then looked at how they responded to the treatment. They analyzed how the expression of 22,000 different genes changed when different cancer cells were given different drugs, and they found that BCL6 levels always rocketed up following treatment.

The BCL6 protein was already known to cancer researchers because it is active in other forms of cancer. In lymphoma, for instance, BCL6 protects cancer cells from dying, and the protein has long been the target for research and drug design. But it had never been connected to leukemia.

Reasoning that blocking BCL6 would make leukemia cells more sensitive to chemotherapy, the scientists showed exactly that. Working with Melnick and colleagues at Weill-Cornell Medical College in New York City who had developed a biotech drug-like peptide that blocks BCL6, they showed that giving the peptide to mice along with anti-leukemia drugs increased the potency of conventional drugs and helped the mice survive the disease.

Now Mschen is looking for ways to do the same thing with small molecules, which are generally easier to formulate into an
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Contact: Jason Socrates Bardi
jason.bardi@ucsf.edu
415-502-4608
University of California - San Francisco
Source:Eurekalert

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