Epigenetic manipulation of leukemia.
Leukemia is a deadly genetic disease of blood cells. Not all leukemias are the same. Some are more amenable to current treatments, while others are not. The underlying mutations in the DNA of the leukemic cells differentiate both the type of leukemia and the response to current treatment. We have analyzed fruit fly genetics to understand essential developmental signals that underlie the genetic changes found in leukemias that do not currently respond to treatment. The genetic pathway we identified is not only conserved from the fruit fly to humans and mice, but it controls an apparently essential cancer-causing signal in leukemic cells. We have devised a mechanism to block this signal, and propose to exploit these novel tools to treat leukemia. Of note, this signal is important in a significant fraction of leukemias from children and adults. In sum, we have uncovered an ancient signaling network that can be inhibited to block leukemia.