Scientists at Northwestern Medicine have discovered two successful therapies that slowed the progression of pediatric leukemia in mice, according to three studies published in the last two years in the journal Cell and the final article published on December 20. Genes and Development.
When a key protein responsible for leukemia, MLL, is stabilized, it slows the progression of leukemia, the latest study found. The next step will be to combine the treatments of the last two years of research into a pediatric leukemia "super-drug" for testing in humans in a clinical trial.
The survival rate is only 30% for children diagnosed with MLL translocation leukemia, a cancer that affects blood and bone marrow. Patients with leukemia have a very low percentage of red blood cells, making them anemic, and have about 80 times more white blood cells than people without cancer.
"These white blood cells infiltrate many of the tissues and organs of affected individuals and is a leading cause of death in patients with leukemia," said senior author Ali Shilatifard, professor of biochemistry and molecular genetics and pediatrics, Robert Francis Furchgott. biochemistry and molecular genetics and director of Simpson's North American Querrey Center for Epigenetics. "This is a monstrous cancer that we have been dealing with for many years with children."
There are several types of leukemia. This research focused on the two most common in adolescent infants: acute myeloid leukemia (AML) and acute lymphocytic leukemia (ALL).
In the last 25 years, the Shilatifard laboratory has been studying the molecular function of MLL within its complex known as COMPASS (Complex Associated Proteins1). More recently, COMPASS components have been shown to be one of the most frequently identified mutations in cancer. The next step in this work will be to get the drug into a clinical testing environment, which Shilatifard said he hopes will happen in the next three to five years.
"I've been working on this translocation for over two decades, and we're finally at the point where, within five to ten years, we can get a drug in children that can be effective," Shilatifard said. "If we can raise the survival rate to 85%, that's a great achievement."
Earlier work from the Shilatifard laboratory published at Cell in 2018 identified compounds that could slow cancer growth by disrupting a gene transcription process known as the "Super Stretch Complex" (SEC). It was the first compound in his class to do this.
This MLL stabilization process discovered in the most recent article could potentially work on cancers with solid tumors, such as breast or prostate cancer, said lead author Zibo Zhao, a postdoctoral researcher at the Shilatifard laboratory.
"This opens a new therapeutic approach not only for leukemia, which is so important for many children who are diagnosed with this terrible cancer but also for other cancers that plague the population," Zhao said.
"The publication of these four articles and the possibility of a future human clinical trial could not have happened had it not been for interdisciplinary collaboration at Northwestern," Shilatifard said.