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Science and Research

Pediatric Leukemia 'Super Drug' Could be Developed in Coming Years

Potential Treatment for Multiple Types of Cancer

This article was originally published in Northwestern Medicine Feinberg School of Medicine News Center. It has been modified for Northwestern Medicine’s content hub, HealthBeat.

Northwestern Medicine scientists have discovered two successful therapies that slow the progression of pediatric leukemia in mice, according to a string of studies published over the last two years in the journal Cell and the final paper recently published in Genes & Development.

According to the most recent study, when a key protein responsible for leukemia, mixed lineage leukemia (MLL), is stabilized, progression of the leukemia slows. The next step will be to combine the treatments from the past two years of research into a pediatric leukemia “super drug” to test on humans in a clinical trial.

About the Findings

Leukemia is cancer of the body’s white blood cells. It occurs when the body overproduces abnormal white blood cells or immature white blood cells. It is the most common cancer in children under 15 years of age. Although there are several types of leukemia, this research focused on the two most frequently found in infants through teenagers: acute myeloid leukemia (AML) and acute lymphocytic leukemia (ALL).

MLL primarily affects newborns and infants. The survival rate is only 30 percent for children diagnosed with MLL-translocation leukemia, a cancer that affects the blood and bone marrow. Individuals with leukemia have a very low percentage of red blood cells, making them anemic, and have approximately 80 times more white blood cells than people without cancer.

“These white blood cells infiltrate many of the tissues and organs of the affected individuals, which is a major cause of death in leukemia patients,” says senior author Ali Shilatifard, PhD, the Robert Francis Furchgott Professor and Chair of Biochemistry and Molecular Genetics and of Pediatrics at Northwestern University Feinberg School of Medicine. “This is a monster cancer that we’ve been dealing with for many years in children.”

For the past 25 years, Dr. Shilatifard’s laboratory has been studying the molecular function of MLL within its complex known as COMPASS (Complex Proteins Associated with Set1). Most recently, COMPASS components were demonstrated to be one of the most frequently identified mutations in cancer. The next step of this work will be to bring the drug to a clinical trial setting, which Dr. Shilatifard says he hopes will happen in the next three to five years.

“I’ve been working on this translocation for more than two decades, and we’re finally at the point where in five to 10 years, we can get a drug in kids that can be effective,” Dr. Shilatifard says. “If we can bring that survival rate up to 85 percent, that’s a major accomplishment.”

Possible Impact on Treatment for Other Types of Cancer

Earlier work from Dr. Shilatifard’s laboratory published in Cell in 2018 identified compounds that could slow cancer growth by interrupting a gene transcription process known as “Super Elongation Complex” (SEC). It was the first compound in its class to do this.

This MLL stabilization process discovered could potentially work in cancers with solid tumors, such as breast or prostate cancer, says first author Zibo Zhao, a postdoctoral research fellow in Dr. Shilatifard’s lab.

“This opens up a new therapeutic approach not only for leukemia, which is so important for the many children who are diagnosed with this terrible cancer, but also for other types of cancers that plague the population,” Zhao says.

“The publication of these four papers and the possibility of a future human clinical trial could not have happened if it weren’t for the cross disciplinary collaboration at Northwestern,” Dr. Shilatifard says.

Robert H. Lurie Comprehensive Cancer Center of Northwestern University