New therapeutic targets and drugs may someday benefit people with certain types of leukemia or blood cancer.

Pre-clinical and pharmacological models found that cancer cells with a mutation in the KIT receptor -- an oncogenic/cancerous form of the receptor -- in mast cell leukemia and acute myeloid leukemia can be stopped.

Activating mutations of KIT receptors are almost always associated with a type of leukemia called mast cell leukemia. The mutations in the KIT receptor are found in about 90 percent of patients with this type of leukemia. In addition, activating mutations of KIT are also exclusively associated with a subtype of acute myeloid leukemia known as core binding factor leukemia. When KIT is associated with these two types of leukemia, the survival rate for patients is profoundly reduced in comparison to patients who do not have this mutation.

The researchers investigated whether they could shut down the growth response that is induced by this mutation.

"We identified two new targets in leukemic cells bearing this mutation, which when targeted or inhibited, cause leukemia cells to die," said Reuben Kapur, Ph.D., a Professor of Pediatrics at
Indiana University.

The researchers discovered that the two targets are Rac GTPase and Pak (p21-activated kinase). In return, they designed a novel Rac inhibitor -- EHop-016 -- that is considerably more potent than previously described inhibitors of Rac. They also demonstrated a novel role for Pak inhibition in leukemia using an existing Pak inhibitor.

Both are being tested in pre-clinical models to further examine their growth inhibitory properties as well as long-term treatment-associated toxicity.

Kapur said treatments for leukemia have remained mostly unchanged in the past 30 years. Thus, researchers continue to search for better and more effective ways to treat this debilitating disease.

"We've been looking for new targets and new ways of treating leukemia and special types of leukemias," Kapur said. "Leukemia is an extremely complex disease. It's a combination of multiple alterations in the patient's DNA, which eventually results in leukemia. Therefore, it will be very difficult to cure leukemia with just one drug. It will have to be a combination of multiple drugs, if we're to cure this disease."

Published in the Journal of Clinical Investigation.