̽��ֱ�� of Cambridge - Brian Huntly

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

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̽��ֱ��Academy of Medical Sciences announces election of new Fellows 2021

cg605 — Wed, 12 May 2021 09:39:48 +0000

̽��ֱ��Academy of Medical Sciences has elected 50 prominent biomedical and health scientists to its respected and influential Fellowship. ̽��ֱ��new Fellows have been selected for their exceptional contributions to the advancement of medical science through innovative research discoveries and translating scientific developments into benefits for patients and the wider society.

Professor Dame Anne Johnson, President of the Academy of Medical Sciences, said: “I am truly delighted to welcome these 50 new Fellows to the Academy’s Fellowship, and I offer my congratulations to each of them on their exceptional contribution to biomedical and health science. ̽��ֱ��knowledge, skill and influence that each brings to the Fellowship is the Academy’s most powerful asset.

“ ̽��ֱ��last year has clearly demonstrated the power and prowess of UK biomedical science, and I am proud of how many Fellows, new and old, have been at the forefront of the COVID-19 response in the UK and globally.

“Although it is hard to look beyond the pandemic right now, I want to stress how important it is that the Academy Fellowship represents the widest diversity of biomedical and health sciences. ̽��ֱ��greatest health advances rely on the findings of many types of research, and on multidisciplinary teams and cross-sector and global collaboration.”

Professor Franklin Aigbirhio FRSC

Professor of Molecular Imaging Chemistry, Department of Clinical Neurosciences and the Department of Chemistry, Senior Research Fellow, Magdalene College

Professor Aigbirhio’s research focuses on the development and application of new biomedical imaging technologies for clinical research in areas such as dementia, acute brain injury and hypertension. His research seeks to enable earlier detection and a greater understanding of the disorders, thereby aiding the development of new treatments. A further objective of Professor Aigbirhio’s work is to enable these new imaging technologies to be more accessible and widely applied throughout the NHS.

“It’s a pleasure and honour to be elected to this Fellowship, which I recognise is an outcome of the collaborations with many talented colleagues at Cambridge and further afield, for which I give my sincere thanks,” said Aigbirhio.

“Going forward my election to the Fellowship provides a platform to highlight the role of black researchers and participants in biomedical and health research and to increase their involvement.”

Professor Ravindra Gupta

Professor of Clinical Microbiology at the Cambridge Institute of Therapeutic Immunology and Infectious Diseases, Fellow, Homerton College

Professor Gupta has worked extensively in HIV, both at molecular and population levels, and his work demonstrating escalating global resistance led to change in WHO treatment guidelines for HIV. He led the team that demonstrated HIV cure in the ‘London Patient’ – only the second in history.

In 2020 he was named as one of the 100 most influential people worldwide by TIME Magazine. Gupta deployed his expertise in RNA virus genetics and biology during the COVID-19 pandemic to report the first evidence for immune escape of SARS-CoV-2 within an individual, defining the process by which new variants likely arise, and also reporting the first data on Pfizer BioNTech vaccine-induced antibody responses against the B.1.1.7 ‘Kent UK’ variant.

“I am honoured to have been elected to Fellowship of the Academy of Medical Sciences,” said Gupta. “ ̽��ֱ��COVID-19 pandemic has demonstrated the importance of cross-disciplinary science. Research excellence across medical sciences and translation to health improvements has been at the centre of the Academy’s mission and I am very pleased to now be able to contribute to fulfilling this aim as a Fellow.”

Professor Brian Huntly

Head of the Department of Haematology and Professor of Leukaemia Stem Cell Biology, Group Leader at the Wellcome – MRC Cambridge Stem Cell Institute

Professor Huntly’s research focuses on the stem cell aspects of the evolution of haematological malignancies, in particular acute myeloid leukaemia and lymphoma. His election recognises his many contributions to the understanding and treatment of blood cancers.

“I am delighted and honoured to be elected to the Fellowship of the Academy of Medical Sciences,” said Huntly. “ ̽��ֱ��Academy’s aims of bringing the best minds in biomedical research together, supporting talent, asking challenging questions and sharing our work so that all can benefit from it mirror very much our own aims here in Cambridge. Biomedical research is a hugely collaborative endeavour and I see my election as recognition of the hard work of many people who have contributed to my research and also highlighting the tremendous work we are doing at the ̽��ֱ�� of Cambridge Department of Haematology.”

Professor Adrian Liston

Senior Group Leader, Babraham Institute, Senior Research Fellow, Churchill College

Professor Adrian Liston works in the field of immunology, based around the question of the biological checkpoints that restrain immune activation. His research investigates the basis for pathological immune activation in the contexts of autoimmune diseases, primary immunodeficiencies and neuroinflammation. By understanding the genetic, molecular and cellular basis of immune checkpoint failure in these conditions, the rationale selection of therapeutics can help prevent or treat pathologies.

“This is a really wonderful recognition of the work from my team”, Liston said. “I’ve been lucky to work with an outstanding team of scientists, able to work on immune pathology from different angles – from the clinic or the lab, as an immunologist or a neuroscientist, in advanced techniques ranging from cytometry through to computational modelling. ̽��ֱ��curiosity and interdisciplinarity of the team are what has let us explore new fields and push the boundaries forwards.”

Professor Benjamin Simons FRS

Royal Society EP Abraham Professor, Department of Applied Mathematics and Theoretical Physics and Senior Group Leader of the Gurdon Institute, Group Leader at the Wellcome – MRC Cambridge Stem Cell Institute, Fellow, St John's College

As a theorist, Professor Simons has contributed to a diverse range of fields, from quantum condensed matter physics to developmental and cancer biology. His research translates concepts and approaches from statistical physics to gain predictive insights in the collective dynamics of complex systems. In biology, his studies have revealed common mechanisms of stem cell regulation, and how these programmes become subverted during the early phase of tumour growth.

Simons said: “As a theorist, and relative newcomer to the field of biomedical sciences, it is a great honour to be elected as a Fellow of the Academy of Medical Sciences.”

Cambridge scientists are among the new Fellows announced today by the Academy of Medical Sciences.

̽��ֱ��greatest health advances rely on the findings of many types of research, and on multidisciplinary teams and cross-sector and global collaboration.

Professor Dame Anne Johnson, President of the Academy of Medical Sciences

̽��ֱ��text in this work is licensed under a Creative Commons Attribution 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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Scientists demonstrate potential new treatment for most common form of infant leukaemia

gm349 — Mon, 03 Oct 2011 08:35:03 +0000

Cambridge scientists have shown that a potential new drug could treat mixed-lineage leukaemia (MLL), the most common form of leukaemia in babies, according to a study published in Nature yesterday (02 October).

MLL leukaemia is thought to account for up to 80 per cent of children below two years of age diagnosed with acute leukaemia, and up to one in 10 cases in adults. Most patients don’t respond well to standard leukaemia treatments and often the cancer comes back.

̽��ֱ��disease is caused when a gene called MLL gets fused to another gene. This disrupts the normal function of MLL by creating a new ‘fusion protein’ that behaves inappropriately, switching on genes that drive the development of leukaemia.

̽��ֱ��research team - based at the Wellcome Trust/Cancer Research UK Gurdon Institute and the Cambridge Institute for Medical Research at the ̽��ֱ�� of Cambridge and with funding from the Cancer Research UK – collaborated with scientists from GlaxoSmithKline (GSK) and Cellzome AG to identify that the MLL-fusion proteins are targeted to leukaemia-causing genes by proteins from the BET family, which recognise certain chemical ‘tags’ on chromatin, the scaffold on which DNA is organised.

Together the researchers showed that a new chemical agent developed by GSK – I-BET151 - mimics these chemical tags, preventing BET and MLL from attaching to chromatin and activating the leukaemia genes. Treatment of leukaemias in mice and human cancer cells in the lab showed that the chemical could halt the disease, paving the way for its use in patient trials.

Study co-leader Professor Tony Kouzarides, deputy director of the Wellcome Trust/Cancer Research UK Gurdon Institute at the ̽��ֱ�� of Cambridge, said: “Our work shows that this type of leukaemia is reliant on MLL being able to bind to chromatin via BET proteins. This “epigenetic” approach to therapy - which targets chromatin rather than DNA - is an exciting new avenue for drug discovery which we hope will be useful for other types of cancer in addition to MLL-leukaemias.”

Dr Brian Huntly, who co-led the study and is based at the Cambridge Institute for Medical Research at the ̽��ֱ�� of Cambridge, said: “MLL leukaemia is very hard to treat and often the only option for patients who have become resistant to standard treatments is a bone marrow transplant. We hope these findings may in future mean that fewer children need this procedure.”

Dr Lesley Walker, Cancer Research UK’s director of cancer information, said: “Cancer Research UK has played an important role in progress being made in childhood leukaemia, with eight in ten children now surviving more than five years compared to fewer than one in ten in the late 1960s. But there is still more work to do and we urgently need better ways to treat children with more aggressive forms of leukaemia, such as MLL. Although this research is only in the lab at the moment, we hope it will move quickly towards clinical trials in patients.”

New drug could treat mixed-lineage leukaemia (MLL).

MLL leukaemia is very hard to treat and often the only option for patients who have become resistant to standard treatments is a bone marrow transplant. We hope these findings may in future mean that fewer children need this procedure.

Dr Brian Huntly, who co-led the study and is based at the Cambridge Institute for Medical Research at the ̽��ֱ�� of Cambridge

Flickr: Amy Loves Yah

Beakers

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