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

used together, issues such as unforeseen toxicity will need to be explored.

We are studying the combination and how it kills, so when the combination goes into the patient, we will be able to get samples from patients, pre- and post-treatment, to see whether what we are observing in the lab works and, if there are patients who still dont respond, why dont they" says Dr. Bhalla.

Histone deacetylase and heat shock protein 90 inhibitors take direct hits at the mutant protein by targeting HSP 90, a molecular chaperone, which, in this case, improperly folds the protein, leaving it active and producing leukemic cells rather than healthy bone marrow cells as needed. Dr. Bhallas lab was the first to show the mutant protein kinase is particularly susceptible to depletion by targeting it with HSP 90 or histone deacetylase inhibitors. He also uncovered the synergy of kinase inhibitors.

We are targeting HSP 90, which folds and keeps this abnormal protein in its active form, he says. By using this agent that targets HSP 90, you also take away many other mechanisms that drive cell proliferation and survival. Once you lower the threshold for cell death by depleting this protein, you use additional strategies to kill leukemic cells. It makes it more effective.


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Contact: Toni Baker
tbaker@mcg.edu
706-721-4421
Medical College of Georgia
Source:Eurekalert

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