Widely used drug could prevent leukaemia among those at risk

A widely used diabetes drug may hold the key to preventing an aggressive form of blood cancer among those at the highest risk, new research suggests.

A study from the University of Cambridge has found that metformin, an inexpensive treatment for type 2 diabetes, could potentially prevent a form of acute myeloid leukaemia (AML) while studying the effects of the drug on mice.

Scientists then analysed genetic data on humans and found that people who were taking metformin were less likely to have a common genetic change linked to AML.

The team focused on a genetic change in a gene called DNMT3A, which has been found to be responsible for starting 10 to 15 per cent of AML cases.

Their work aimed to investigate how to prevent abnormal blood stem cells with genetic changes from progressing to become AML.

Blood stem cells in mice with the same changes in DNMT3A depend more on a process called mitochondrial metabolism, compared to healthy cells, making this a target for research, they said.

The scientists found that in mice, metformin and other drugs which impact mitochondrial metabolism substantially slowed the growth of blood cells with the mutation in the gene, according to the study published in the journal Nature.

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Further lab experiments also showed that metformin could have the same effect on human blood cells with the DNMT3A mutation.

Researchers then analysed data from 412,000 people taking part in the UK Biobank study and found that people taking metformin were less likely to have changes in the DNMT3A gene.

Around 3,100 people are diagnosed with AML each year in the UK, and the disease has low survival rates.

People at high risk of AML can be identified years in advance but there is no treatment that can prevent the disease from developing.

Professor George Vassiliou, from the Cambridge Stem Cell Institute at the University of Cambridge and Cambridge University Hospitals NHS Foundation Trust, who co-led the study, said: “Blood cancer poses unique challenges compared to solid cancers like breast or prostate, which can be surgically removed if identified early.

“With blood cancers, we need to identify people at risk and then use medical treatments to stop cancer progression throughout the body.”

First author of the study Dr Malgorzata Gozdecka added: “Metformin is a drug that impacts mitochondrial metabolism, and these pre-cancerous cells need this energy to keep growing.

“By blocking this process, we stop the cells from expanding and progressing towards AML, whilst also reversing other effects of the mutated DNMT3A gene.”

Dr Rubina Ahmed, director of research at Blood Cancer UK, which part-funded the work, said: “Blood cancer is the third biggest cancer killer in the UK, with over 280,000 people currently living with the disease.

“Our blood cancer action plan shed light on the shockingly low survival for acute myeloid leukaemia, with only around two in 10 surviving for five years, and we urgently need better strategies to save lives.

“Repurposing safe, widely available drugs like metformin means we could potentially get new treatments to people faster, without the need for lengthy drug development pipelines.”

Tanya Hollands, from Cancer Research UK, which also part-funded the work, added: “It’s important that we work to find new ways to slow down or prevent AML in people at high risk.

“Therefore, it’s positive that the findings of this study suggest a possible link between a commonly used diabetes drug and prevention of AML progression in some people.

“While this early-stage research is promising, clinical trials are now needed to find out if this drug could benefit people. We look forward to seeing how this work progresses.”

The next phase of the work will focus on clinical trials to test metformin’s effectiveness in people with changes in DNMT3A at increased risk of developing AML.