Mount Sinai Scientists Show That a Novel Therapy Could Be Effective Against Pediatric Leukemia
Therapy could also fight pancreatic and other cancers, researchers say
Mount Sinai researchers have developed a therapy that shows promise against a deadly pediatric leukemia. The small-molecule therapy was highly effective in fighting a type of acute myeloid leukemia in both in vitro and in vivo experiments, according to research published in Science Translational Medicine in September.
The therapy, named MS67, causes the degradation of the WDR5 protein, which drives the proliferation of acute myeloid leukemia with a specific genetic makeup called mixed lineage leukemia rearrangement. This type of leukemia is more common in children, has very poor response to standard treatments and a dismal prognosis, and until now has confounded researchers.
WDR5 also plays an important role in driving the proliferation of other cancers such as pancreatic cancer, so researchers believe that it is likely that WDR5 small-molecule degraders such as MS67 could also be effective in treating those cancers.
“This study is the first to demonstrate that pharmacological degradation of WDR5, which selectively eliminates the proten, is an effective and superior therapeutic strategy than pharmacological inhibition, or blocking, of WDR5 for the treatment of WDR5-dependent cancers including acute myeloid leukemia with mixed lineage leukemia rearrangement,” said Jian Jin, PhD, the Mount Sinai Professor in Therapeutics Discovery and Director of the Mount Sinai Center for Therapeutics Discovery at the Icahn School of Medicine at Mount Sinai. “In addition, MS67 is the first WDR5 small-molecule degrader that exhibits robust anti-tumor activities in vivo.”
The research team led by Dr. Jin; Greg Wang, PhD, of the University of North Carolina at Chapel Hill; and Aneel Aggarwal, PhD, Professor of Pharmacological Sciences, and Oncological Sciences, at The Tisch Cancer Institute at Mount Sinai, discovered MS67, a novel, highly potent and selective small-molecule degrader of WDR5, which effectively suppressed the growth of this type of acute myeloid leukemia cells derived from patients both in vitro and in vivo, using patient cancer cells in mouse models. Using a battery of biochemical, biophysical, structural, cellular, genomic, and in vivo studies, the research team demonstrated that MS67 is a much superior therapeutic agent than other therapies that inhibit instead of degrade WDR5.
This research was supported in part by the grants R01GM122749, P30CA196521, R01CA211336, R01CA215284, and R35GM131780 from the U.S. National Institutes of Health.
About the Mount Sinai Health System
Mount Sinai Health System is one of the largest academic medical systems in the New York metro area, with more than 43,000 employees working across eight hospitals, over 400 outpatient practices, nearly 300 labs, a school of nursing, and a leading school of medicine and graduate education. Mount Sinai advances health for all people, everywhere, by taking on the most complex health care challenges of our time — discovering and applying new scientific learning and knowledge; developing safer, more effective treatments; educating the next generation of medical leaders and innovators; and supporting local communities by delivering high-quality care to all who need it.
Through the integration of its hospitals, labs, and schools, Mount Sinai offers comprehensive health care solutions from birth through geriatrics, leveraging innovative approaches such as artificial intelligence and informatics while keeping patients’ medical and emotional needs at the center of all treatment. The Health System includes approximately 7,300 primary and specialty care physicians; 13 joint-venture outpatient surgery centers throughout the five boroughs of New York City, Westchester, Long Island, and Florida; and more than 30 affiliated community health centers. We are consistently ranked by U.S. News & World Report's Best Hospitals, receiving high "Honor Roll" status, and are highly ranked: No. 1 in Geriatrics and top 20 in Cardiology/Heart Surgery, Diabetes/Endocrinology, Gastroenterology/GI Surgery, Neurology/Neurosurgery, Orthopedics, Pulmonology/Lung Surgery, Rehabilitation, and Urology. New York Eye and Ear Infirmary of Mount Sinai is ranked No. 12 in Ophthalmology. U.S. News & World Report’s “Best Children’s Hospitals” ranks Mount Sinai Kravis Children's Hospital among the country’s best in several pediatric specialties. The Icahn School of Medicine at Mount Sinai is one of three medical schools that have earned distinction by multiple indicators: It is consistently ranked in the top 20 by U.S. News & World Report's "Best Medical Schools," aligned with a U.S. News & World Report "Honor Roll" Hospital, and top 20 in the nation for National Institutes of Health funding and top 5 in the nation for numerous basic and clinical research areas. Newsweek’s “The World’s Best Smart Hospitals” ranks The Mount Sinai Hospital as No. 1 in New York and in the top five globally, and Mount Sinai Morningside in the top 20 globally.