Investigators at the Northwestern University Feinberg School of Medicine have presented new data that shows when a key protein responsible for leukemia—dubbed mixed-lineage leukemia 1 (MLL1)—is stabilized; it slows the progression of the disease. This is the second successful therapy that slowed the progression of pediatric leukemia in mice, according to three studies published over the last two years. Findings from this most recent study were published in Genes & Development through an article titled “Regulation of MLL/COMPASS stability through its proteolytic cleavage by taspase1 as a possible approach for clinical therapy of leukemia.”

The survival rate is only 30% for children diagnosed with MLL-translocation leukemia, a cancer that affects the blood and bone marrow. Patients 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. The researchers are optimistic that 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.

“These white blood cells infiltrate many of the tissues and organs of the affected individuals and are a major cause of death in leukemia patients,” explained senior study investigator Ali Shilatifard, Ph.D., professor, and director of Northwestern’s Simpson Querrey Center for Epigenetics. “This is a monster cancer that we’ve been dealing with for many years in children.”

While there are several types of leukemia, this current study focused on the two most commonly found in infants through teenagers: acute myeloid leukemia (AML) and acute lymphocytic leukemia (ALL).

Over 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, it was demonstrated that COMPASS components are 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 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 5 to 10 years, we can get a drug in kids that can be effective,” Dr. Shilatifard noted. “If we can bring that survival rate up to 85%, that’s a major accomplishment.”

Previous work from the research group 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.

The MLL stabilization process discovered in this most recent study could potentially work in cancers with solid tumors, such as breast or prostate cancer.

“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,” concluded lead study investigator Zibo Zhao, Ph.D., a postdoctoral research fellow in Dr. Shilatifard’s laboratory.

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