̽��ֱ�� of Cambridge - George Vassiliou

Mouse study suggests a common diabetes drug may prevent leukaemia

cjb250 — Wed, 16 Apr 2025 07:59:00 +0000

Around 3,100 people are diagnosed with acute myeloid leukaemia (AML) each year in the UK. It is an aggressive form of blood cancer that is very difficult to treat. Thanks to recent advances, individuals at high risk of AML can be identified years in advance using blood tests and blood DNA analysis, but there’s no suitable treatment that can prevent them from developing the disease.

In this study, Professor George Vassiliou and colleagues at the ̽��ֱ�� of Cambridge investigated how to prevent abnormal blood stem cells with genetic changes from progressing to become AML. ̽��ֱ��work focused on the most common genetic change, which affects a gene called DNMT3A and is responsible for starting 10-15% of AML cases.

Professor Vassiliou, from the Cambridge Stem Cell Institute at the ̽��ֱ�� of Cambridge and Honorary Consultant Haematologist at Cambridge ̽��ֱ�� Hospitals NHS Foundation Trust (CUH) co-led the study. He 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.”

̽��ֱ��research team examined blood stem cells from mice with the same changes in DNMT3A as seen in the pre-cancerous cells in humans. Using a genome-wide screening technique, they showed that these cells depend more on mitochondrial metabolism than healthy cells, making this a potential weak spot. ̽��ֱ��researchers went on to confirm that metformin, and other mitochondria-targeting drugs, substantially slowed the growth of mutation-bearing blood cells in mice. Further experiments also showed that metformin could have the same effect on human blood cells with the DNMT3A mutation.

Dr Malgorzata Gozdecka, Senior Research Associate at the Cambridge Stem Cell Institute and first author of the research said: “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.”

In addition, the study looked at data from over 412,000 UK Biobank volunteers and found that people taking metformin were less likely to have changes in the DNMT3A gene. This link remained even after accounting for factors that could have confounded the results such as diabetes status and BMI.

Professor Brian Huntly, Head of the Department of Haematology at the ̽��ֱ�� of Cambridge, Honorary Consultant Haematologist at CUH, and joint lead author of the research, added: “Metformin appears highly specific to this mutation rather than being a generic treatment. That specificity makes it especially compelling as a targeted prevention strategy.

“We’ve done the extensive research all the way from cell-based studies to human data, so we’re now at the point where we have a made a strong case for moving ahead with clinical trials. Importantly, metformin’s lack of toxicity will be a major advantage as it is already used by millions of people worldwide with a well-established safety profile.”

̽��ֱ��results of the study, funded by Blood Cancer UK with additional support from Cancer Research UK, the Leukemia & Lymphoma Society (USA) and the Wellcome Trust, are published in Nature.

Dr Rubina Ahmed, Director of Research at Blood Cancer UK, 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 2 in 10 surviving for 5 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.”

̽��ֱ��next phase of this research will focus on clinical trials to test metformin’s effectiveness in people with changes in DNMT3A at increased risk of developing AML. With metformin already approved and widely used for diabetes, this repurposing strategy could dramatically reduce the time it takes to bring a new preventive therapy to patients.

Tanya Hollands, Research Information Manager at Cancer Research UK, who contributed funding for the lab-based screening in mice, said: “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.”

Reference
Gozdecka, M et al. Mitochondrial metabolism sustains DNMT3A-R882-mutant clonal haematopoiesis. Nature; 16 Apr 2025; DOI: 10.1038/s41586-025-08980-6

Adapted from a press release from Blood Cancer UK

Metformin, a widely used and affordable diabetes drug, could prevent a form of acute myeloid leukaemia in people at high risk of the disease, a study in mice has suggested. Further research in clinical trials will be needed to confirm this works for patients.

We’ve done the extensive research all the way from cell-based studies to human data, so we’re now at the point where we have a made a strong case for moving ahead with clinical trials

Brian Huntly

̽��ֱ�� of Cambridge

Brown lab mouse on blue gloved hand

̽��ֱ��text in this work is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International License. Images, including our videos, are Copyright © ̽��ֱ�� of Cambridge and licensors/contributors as identified. All rights reserved. We make our image and video content available in a number of ways – on our main website under its Terms and conditions, and on a range of channels including social media that permit your use and sharing of our content under their respective Terms.

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Scientists develop test to identify people at risk of developing acute myeloid leukaemia and related cancers

jg533 — Thu, 24 Aug 2023 15:14:28 +0000

Researchers at the Wellcome-MRC Cambridge Stem Cell Institute (CSCI), the ̽��ֱ�� of Cambridge’s Department of Haematology, and Instituto de Investigación Sanitaria del Principado de Asturias (ISPA) analysed data from more than 400,000 individuals participating in the United Kingdom Biobank.

Using this data, the scientists created 'MN–predict', a platform for predicting the risk of developing blood cancers such as acute myeloid leukaemia, myelodysplastic syndromes and myeloproliferative neoplasms over a 10- to 15-year period.

̽��ֱ��test, now available in NHS clinics, requires patients to provide a blood sample from which DNA is extracted for limited sequencing, alongside basic blood cell counts. With this information, MN-predict identifies those at high risk of any of these cancers and can be used in specialist clinics for leukaemia prevention.

Professor George Vassiliou, senior author of the study, said: “We all know that prevention is better than cure, but it is not easy to prevent diseases like leukaemia without knowing who is at risk. MN-predict makes it possible to identify at-risk individuals, and we hope it can become an essential part of future leukaemia prevention programmes.”

̽��ֱ��myeloid neoplasms are a group of related cancers encompassing acute myeloid leukaemia, myelodysplastic syndromes and myeloproliferative neoplasms. Treatments for these cancers have improved in the last few years, but most cases remain incurable.

In the last few years, scientists have discovered that these cancers develop over decades through the accumulation of DNA mutations in blood stem cells - the cells responsible for normal blood formation. ̽��ֱ��mutations encourage these stem cells to grow faster than normal and, as more mutations accumulate, they can progress towards leukaemia.

While mutations that promote cell growth are common, leukaemia develops only in a small minority of cases. Identifying these cases early on helps efforts to prevent the cancers from developing.

̽��ֱ��work is published today in the journal Nature Genetics.

Dr Muxin Gu, first author of the paper, said: “We hope that MN-predict will help clinicians to identify people at risk of myeloid cancers, and use novel treatment to prevent the cancers developing.”

Dr Pedro M Quiros, joint senior author of the study, said: “Despite some recent advances in their treatment, unfortunately these cancers remain lethal to many sufferers. We hope that our efforts will help advance prevention in favour of treating the full-blown disease.”

̽��ֱ��research and development of MN-Predict was funded by Cancer Research UK and the Leukaemia and Lymphoma Society. Scientists from the Early Cancer Institute, ̽��ֱ�� of Cambridge, ̽��ֱ�� of Bristol, ̽��ֱ�� of Oviedo (Spain), ̽��ֱ�� of York, AstraZeneca (UK), German Cancer Research Center (DKFZ, Germany), St James's Hospital, Leeds (UK) and ̽��ֱ�� of Pavia (Italy) also participated in the study.

Reference

Gu M, Cheloor-Kovilakam S, Dunn W, Marando L, Barcena C, Mohorianu I, Smith A, Kar S, Fabre M, Gerstung M, Cargo C, Malcovati L, Quiros P, Vassiliou G: 'Multiparameter prediction of myeloid neoplasia risk.' Nature Genetics. 2023. DOI: 10.1038/s41588-023-01472-1

Adapted from a press release by the Wellcome-MRC Cambridge Stem Cell Institute.

̽��ֱ��new ‘MN-predict’ platform will allow doctors and scientists to identify those at risk and to design new treatments to prevent them from developing these potentially lethal cancers.

MN-predict makes it possible to identify at-risk individuals, and we hope it can become an essential part of future leukaemia prevention programmes.

George Vassiliou

Nguyễn Hiệp on Unsplash

Person having a blood test

̽��ֱ��text in this work is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International License. Images, including our videos, are Copyright © ̽��ֱ�� of Cambridge and licensors/contributors as identified. All rights reserved. We make our image and video content available in a number of ways – as here, on our main website under its Terms and conditions, and on a range of channels including social media that permit your use and sharing of our content under their respective Terms.

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