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Novel strategy under study for aggressive leukemia
Date:9/24/2007

A novel strategy to hopefully beat into oblivion one of the most aggressive forms of acute myelogenous leukemia combines the strengths of some of the newest leukemia agents, researchers say.

These are not traditional chemotherapy regimens. These are targeted therapies that our earlier laboratory studies have shown have a synergistic effect, says Dr. Kapil N. Bhalla, director of the Medical College of Georgia Cancer Center.

The strategy takes on the mutated protein receptor that enables the deadly proliferation of leukemic cells by degrading it with histone deacetylase and heat shock protein 90 inhibitors. It uses protein kinase inhibitors to reduce the function of any remaining protein and kills off leukemic cells with a natural cell death mechanism called TRAIL.

Dr. Bhalla recently received a five-year, $1.3 million grant from the National Cancer Institute that will enable his research team to do more preclinical testing of the strategy in human leukemic cells and an AML animal model.

About six years ago, researchers found the mutation in the FLT-3 gene that results in the mutated protein receptor on the cell surface. This receptor usually responds to a growth factor that gives rise to normal bone marrow cell proliferation. But in this case, this mutated protein receptor is constantly triggered, is constantly on and it drives proliferation, promotes survival and shuts down differentiation, Dr. Bhalla says.

Within weeks, leukemic cells take over the bone marrow, then spread throughout the body. Patients typically develop abnormalities of white blood cell count and platelet count, anemia or weakness and present with either an infection because they dont have enough white blood cells or bleeding, he says.

We dont know what causes these mutations, but if you have FLT-3 mutation about 30 percent of AML patients do then the leukemia is generally more aggressive, says Dr. Bhalla. For whatever reason, this
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Contact: Toni Baker
tbaker@mcg.edu
706-721-4421
Medical College of Georgia
Source:Eurekalert

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