Greek Scientists Find Unexpected Drug Target for Acute Myeloid Leukemia

Greek scientists found an unexpected new drug target for acute myeloid leukemia (AML) that could open new avenues to develop effective treatments against the potentially lethal disease.

(AML) is an aggressive blood cancer that affects people of all ages, often requiring months of intensive chemotherapy and prolonged hospital admissions. It develops in cells in the bone marrow crowding out the healthy cells, in turn leading to life-threatening infections and bleeding.

According to the news-medical.net, researchers from the Wellcome Trust Sanger Institute, the Gurdon Institute, and their collaborators show that inhibiting the METTL3 gene destroys human and mouse AML cells without harming non-leukemic blood cells.

The study results appeared in the journal Nature on Monday, revealing why METTL3 is required for AML cell survival, by deciphering the new mechanism it uses to regulate several other leukemia genes.

To identify potential new ways to treat AML, the researchers used CRISPR-Cas9 gene-editing technology to screen cancer cells for vulnerable points. They created mouse leukemia cells with mutations in the genes that may be targeted in human AML cells and systematically tested each gene, finding which were essential for AML survival, the news-medical.net report says.

Professor Tony Kouzarides; joint project leader from the Gurdon Institute, University of Cambridge, said: “New treatments for AML are desperately needed and we have been looking for genes that would be good drug targets. We identified the methyltransferase enzyme METTL3 as a highly viable target against AML. Our study will inspire pharmaceutical efforts to find drugs that specifically inhibit METTL3 to treat AML.”

Dr Konstantinos Tzelepis; from the Wellcome Trust Sanger Institute, said: “This study uncovered an entirely new mechanism of gene regulation in AML that operates through modifications of RNA. We discovered that inhibiting the methyltransferase activity of METTL3 would stop the translation of a whole set of proteins that leukemia needs. This mechanism shows that a drug to inhibit methylation could be effective against AML without affecting normal cells.”

Dr George Vassiliou; joint project leader from the Sanger Institute and Consultant Haematologist at Cambridge University Hospitals NHS Trust, said: “AML is a feared disease that affects people all around the world, our treatments have changed little for decades and outcomes remain poor for the majority of patients. We believed that we had to think differently and look in new places for ways to treat the disease and in METTL3 we have found an exciting new target for drugs. We hope that this discovery will lead to more effective treatments that will improve the survival and the quality of life of patients with AML.”