The researchers treated mice genetically engineered to have JMML with a drug that inhibits a signaling protein called MEK. The drug, known as a MEK inhibitor, blocks just one of the many chemical pathways controlled by Ras. Although several pharmaceutical companies already are developing these drugs, this is the first time a MEK inhibitor has been piloted as a treatment for JMML.
Remarkably, within one week of starting treatment, leukemia symptoms in nearly all of the afflicted mice reversed. Specifically, mice that were treated with the MEK inhibitor produced more red blood cells and fewer white blood cells than untreated mice, and the anemia commonly associated with JMML also disappeared.
According to the researchers, a particularly compelling aspect of the findings is that even after treatment, the majority of the animals' blood was still being produced by the mutant cells that previously caused the disease.
"The most striking aspect of our findings was that the treatment helped the mice not by making the cancer cells go away, but by forcing them to act like normal cells, despite their mutation," said first author Natalya Lyubynska, MD, an internal medicine resident at the University of Michigan. Lyubynska completed this research in Braun's lab as a UCSF medical student, with support from the UCSF Helene and Charles Linker Fellowship and was awarded the UCSF Dean's Prize for Outstanding Student Research for this work.
Through the positive effects of treatment, the study also helps clarify the mechanism by which the Ras signaling pathway regulates cell growth and confirms that the MEK protein plays a key role in the development of JMML.
"It appears that Ras causes disease in part by producing an imbalance of the kinds of cells made in the bone marrow, and that inhibiting MEK can reverse that process," Braun said. "We hop
|Contact: Kate Vidinsky|
University of California - San Francisco