"We are on the brink of a very exciting time for the treatment of leukemia," Bushweller said. "Our goal is to develop new drugs that encourage specific molecules to inhibit certain altered proteins that arise in leukemia patients. If we can selectively inhibit these proteins, we hope that leukemia can be shut down. Since the molecules are selective, the side effects of treatment and the long-term prognosis for leukemia patients should be significantly better than they are today."
Bushweller also expects the grant to create about eight new research jobs at the U.Va. Health System.
He cites the success of the targeted chemotherapy drug Gleevec for chronic myelogenous leukemia as a powerful example of the potential of this targeted approach. "Our project is based on this concept," Bushweller said. "We hope that our research will make it to clinical trials in patients and prove to be a highly effective weapon in the treatment of leukemia."
Bushweller's group will use three-dimensional structures and computational methods, in combination with screening, to develop small molecules synthesized by Brown's lab that will bind at a desired site on the altered proteins that arise in leukemia and inhibit the proteins.
The grant from the Leukemia and Lymphoma Society is called a Specialized Center of Research (SCOR) grant. "The cornerstone of the SCOR program is its collaborative structure, "said Alan Kinniburgh, Ph.D., senior vice president of research at the Society. "Every recipient works with a cross-disciplinary team of leading researchers from their own and other universities and medical institutions. The concept is that leukemia, lymphoma and myeloma treatments and cures will be discovered most quickly in an environment of collaboration and teamwork."
The Bushweller team at the U.Va. Health System is working in collaboration with Dr. D. Gary Gilliland, M.D., Ph.D., at Harvard Medical School, Dr. P. Paul Liu, M.D., Ph.D., at the National Human Genome Institute of the National Institutes of Health and Nancy Speck, Ph.D., at Dartmouth Medical School.
A second $5 million, 5-year SCOR grant has also been awarded to Tak Mak, Ph.D., professor of immunology and medical biophysics at the University of Toronto. He is studying signaling pathways in leukemia- and lymphoma- genesis.
Leukemia is characterized by the uncontrolled accumulation of blood cells. The disease is divided into myelogenous and lymphocytic leukemia, each of which can be acute or chronic. About 33,440 new cases of leukemia will be diagnosed in the U.S. this year, mostly in older adults. However, leukemia makes up about 30 percent of all cancers in children. The relative five-year survival rate for people with leukemia has more than tripled in recent decades to 46 percent. Still, according to The Leukemia and Lymphoma Society, about 23,300 people are expected to die of leukemia in the U.S. this year alone.