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Greek scientists make promising breakthrough for leukaemia patients

A new study has isolated a gene which, when targeted with drugs, leads leukaemia cells to start dying

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Photo: The Whistler

07 December 2017

After decades of largely unchanged treatments, a new study led by Greek scientists is showing great promise for leukaemia patients, revealing a gene that 'blocks' the disease.

Reported in the scientific journal Nature late last month, researchers from the Wellcome Trust Sanger Institute, the Gurdon Institute and their collaborators show that inhibiting the METTL3 gene with certain drugs destroys the cells of acute myeloid leukemia (AML) - an aggressive cancer of the blood - without negatively impacting non-leukemic blood cells.

The study goes on to reveal why METTL3 is required for AML cell survival, by deciphering the new mechanism it uses to regulate several other leukaemia genes.CRISPR-Cas9 gene-editing technology was used to screen cancer cells for vulnerabilities. These leukaemia cells with mutations in the genes were then created in mice, with each gene tested in a bid to find which were essential for the leukaemia's survival.

"This mechanism shows that a drug to inhibit methylation could be effective against AML without affecting normal cells," said one of the study's authors, Dr Konstantinos Tzelepis.

They ended up with 46 possible genes, but it was METTL3 that was found to have the strongest effect. The real breakthrough came when they discovered that while it was essential to the survival of the leukaemia cells, it was not required for healthy blood cells.

Joint project leader, Professor Tony Kouzarides stressed the importance of new treatments for AML and said that their study "will inspire pharmaceutical efforts to find drugs that specifically inhibit METTL3 to treat AML".

AML is a cancer that affects people of all ages. The condition develops in cells in the bone marrow crowding out the healthy cells, in turn leading to life-threatening infections and bleeding. With patients often requiring months of intensive chemotherapy and prolonged hospital admissions, outcomes are currently poor for the majority, but joint project leader Dr George Vassiliou is positive about the future thanks to their innovative approach.

"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," he said.

"We hope that this discovery will lead to more effective treatments that will improve the survival and the quality of life of patients."

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