Yubin Ge, Ph.D.
Chengzhi Xie, Ph.D.
Yubin Ge, Ph.D., and Chengzhi Xie, Ph.D., presented a poster at the conference revealing that a combination of FDA-approved drugs works synergistically to help children with acute myeloid leukemia.
Dr. Ge is an assistant professor with the Wayne State University School of Medicine’s Department of Pediatrics and Karmanos. Dr. Xie is a Postdoctoral Fellow with the Developmental Therapeutics Program at Karmanos Cancer Institute and Wayne State University School of Medicine. He also is a lecturer with the College of Life Science at Jilin University in Changchun, China.
AML, which originates in bone marrow, accounts for one-fourth of acute leukemia in children and is responsible for more than half of the leukemia deaths in this population. Approximately 600 children are diagnosed with AML each year, said Dr. Ge, and there is no effective drug treatment for those children should they relapse.
“Right now, we are at a bottleneck,” Dr. Ge said. “We really want to find a better treatment for those relapsed cases.”
Dr. Ge and fellow researchers considered drugs that are already FDA-approved to help fight AML. Resistance among patients to FDA-approved cytarabine is a major cause of treatment failure in AML. Scientists considered clofarabine, approved by the FDA in 2004, and paired it with valproic acid, typically used to treat epilepsy. They found the two drugs worked together to dramatically stimulate cell death.
“We considered an old drug for a new use,” Dr. Ge said. “It looks like the increased drug activity or synergy is not due to the transport or delivery of clofarabine, but to enhanced cell death. We were so pleased with the results.”
AML afflicts mostly adults – about 10,000 new cases each year – and strikes older children. Acute lymphoblastic leukemia usually affects children between the ages of 2 and 5 and is generally easier to treat. Treatment advancements for AML, however, have been less successful.
Dr. Ge said researchers discovered the synergy between valproic acid and clofarabine only a few months ago, though departmental research has spanned some 15 years in the field of treating childhood leukemia. The current research represents a unique partnership between Dr. Ge, his Karmanos colleagues, and Jeffrey W. Taub, M.D., a pediatric oncologist at Children’s Hospital of Michigan and associate professor with the School of Medicine.
Dr. Ge expects the findings will move into the clinical phase in the next few years. St. Jude Children’s Research Hospital in Memphis, Tenn., is now conducting its own clinical drug trial studying the combined effects of valproic acid and cytarabine to treat newly diagnosed AML patients 21 and younger.
“This is truly translational research,” Dr. Ge said. “We really want to translate what we do in the laboratory to the clinic and hopefully save more lives.”