Pursuing a Better Understanding of Childhood Leukemia
by John H. Kersey, M.D.
Researchers at the University of Minnesota are developing new treatments for hard-to-treat infant leukemia.
Leukemias which develop in infants are very difficult to treat. Our research team at the University of Minnesota is making progress using blood or marrow transplantation and new forms of chemotherapy. However, we need a better understanding of what it is about this relatively rare form of leukemia that makes it treatment resistant.
Our research activities focus on:
- Understanding the genetic events that occur in infants with leukemia.
- Developing new treatment methods by growing leukemia cells.
Infant leukemias usually develop before the baby is born. Children’s Cancer Research Fund Chief Medical Advisor, Dr. Julie Ross is investigating potential causes of infant leukemia. She has found potential connections between maternal exposures and the risk of developing infant leukemia.
Unraveling the Genetic Make-Up that Results in Cancer
Our laboratory, and others around the world, are looking at what happens at the genetic level that results in cancer in babies. We have found that infant leukemia occurs most often because DNA is broken at very specific sites within two genes, called MLL and AF4. Portions of these two genes come together to form a new gene called MLL-AF4. This new gene produces a protein that causes cells to become cancerous.
Our laboratory studies normal MLL and AF4 genes as well as the leukemia-producing MLL-AF4 gene. We believe that the normal genes help determine how and when a cell:
- Divides.
- Matures into a specific type of white blood cell.
- Dies or "self-destructs."
Most abnormal cells never mature. Instead, they self-destruct, which is nature's way of eliminating unwanted cells.
We believe that the abnormal MLL-AF4 gene alters decisions that determine the fate of the cell. We have recently discovered that leukemia cells with the MLL-AF4 gene have lost the ability to self-destruct and instead continue to divide, resulting in cancer.
"Turning off" the Cancer Gene
With a greater understanding of how these cells, genes, and proteins work, we are able to investigate potential treatment strategies. For example, antibodies produced in our laboratory can target MLL-AF4 proteins and help to explain how the cellular processes of these abnormal genes work. We hope to eventually find ways to turn off the MLL-AF4 cancer-inducing gene.
By growing leukemia cells in mice and giving them various forms of antibodies, immune cells, or chemotherapeutic drugs, we can study ways to treat the difficult MLL-AF4 leukemia. Laboratory research should help us better predict which treatments may be more effective for children suffering from difficult to treat infant leukemia.
