Protein Pickoff

Targeted agent prolongs survival in chronic leukemia model

Amy JohnsonCurrent therapies for human chronic lymphocytic leukemia (CLL) often damage the immune system, leading to infections that are the primary cause of death for these patients.

But an experimental oral agent called 17-DMAG may help overcome this problem, according to a study by researchers at the OSUCCC – James.

The laboratory and animal findings indicate that this agent is highly selective for CLL cells and has minimal effect on normal immune cells, suggesting that it may leave a patient’s immune system healthy, the researchers say.

“This agent turns off multiple proteins that cancer cells need to survive, and we show that this activity occurs both in CLL cells from patients and in a CLL mouse model,” says study leader Amy Johnson, PhD. “Our findings strongly support testing this agent in CLL patients in a phase I clinical trial.”

The research showed that the drug significantly prolonged survival in a CLL mouse model. Animals treated with the agent survived an average of 75 days, compared with 66 days for animals that didn’t receive it.

The agent works by inhibiting the action of protein HSP90, which is active mainly in CLL cells. This protein accompanies and protects other proteins as they are being made by CLL cells.

These other proteins include AKT, RAF and Zap-70, all of which are important for the survival and growth of the cancer cells. Blocking the protective protein leads to destruction of the other proteins.

In addition, the agent reactivates a gene called FOXD3. This same research group showed in previous work that FOXD3 is silenced early during human CLL development, a change that likely plays an important role in CLL progression.

Presented at the 51st Annual Meeting of the American Society of Hematology, December 2009.

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