Northwestern Medicine scientists have discovered two successful therapies that slowed the progression of pediatric leukaemia in mice, according to three studies published over the last two years in the journal Cell, and the final paper published Dec. 20 in Genes & Development.
There are several types of leukaemia. This research focused on the two most commonly found in infants through teenagers: acute myeloid leukaemia (AML) and acute lymphocytic leukaemia (ALL).
For the past 25 years, 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 Shilatifard said 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,” Shilatifard said. “If we can bring that survival rate up to 85%, that’s a major accomplishment.”
Earlier work from 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 in the most recent paper could potentially work in cancers with solid tumours, such as breast or prostate cancer, said first author Zibo Zhao, a postdoctoral research fellow in Shilatifard’s lab.
“This opens up a new therapeutic approach not only for leukaemia, 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 said.
“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,” Shilatifard said.
Source: Genes & Development
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