It may be possible to identify which pre-cancerous cells will develop into a rare type of blood cancer, due to new research showing that a single genetic change drives myeloid leukaemia in children with Down syndrome 1 .
An international team, including those at the Wellcome Sanger Institute, Great Ormond Street Hospital, Goethe University Frankfurt, Cambridge University Hospitals, and their collaborators, investigated the differences between cancer cells and pre-cancer cells, which appear the same under the microscope, to understand why some develop into cancer and others do not.
The paper, published today (23 April) in Nature Communications , identified the main changes that drive the transition of normal cells to cancer, revealing a possible genetic Achilles’ heel.
Children with Down syndrome have a 150-fold increased risk of developing myeloid leukaemia (ML-DS), despite having a lower risk of other cancers 2 . Myeloid leukaemia in these children arises from a pre-cancer state, known as transient abnormal myelopoiesis (TAM), which 15 to 30 per cent of children with Down syndrome are born with 3 . TAM cells have a conserved set of molecular changes that cause cell growth, but additional changes are needed to drive the development of cancer.
Understanding the molecular factors that lead to ML-DS could help identify children at risk and highlight whether any of the changes are the same as those in other cancers, potentially opening the door to repurposing existing treatments.
This new research was the first of its kind to map the evolution of ML-DS in this context. Researchers used in-depth genomic techniques to see which genetic changes were specific to ML-DS and TAM cells, and how other changes in the cell might drive the development of cancer.
The team found that the molecular backbone of all stages of this blood cancer, both pre-cancerous TAM and developed ML-DS, is very similar, providing a common vulnerability and treatment target.
It has been known that a specific change in the GATA1 gene is present in all stages of the disease. However, when TAM progresses to ML-DS, additional genetic changes occur. In this study, the team found that despite these additional changes, GATA1 -induced molecular differences are present at all stages. As this seems to be the most impactful genetic change, the researchers suggest that it could be possible to develop a therapy that targets this in the future.
While both ML-DS and TAM look the same under the microscope, the team found that they generated different transcriptional data, which gives information about what genes are active in the cell at a given time. This also allowed them to predict which TAM cells would become cancerous. With further research, this could be a clinically relevant biomarker in the future for identifying those children at higher risk of developing this cancer.
Dr Jack Bartram, co-senior author at Great Ormond Street Hospital, said: “This is the first time that it has been possible to investigate the full evolution of pre-cancer to cancer cells in the context of ML-DS. Rare cancers impact the lives of children and families around the world, and research is the only way that we will find answers that can help inform new approaches and treatments.”
Professor Jan-Henning Klusmann, co-senior author at the Goethe University Frankfurt, said: “While it has been previously known that there is an increased risk of myeloid leukaemia in children with Down syndrome, the underlying genetic programmes were obscure. Although further investigation is needed before this can have clinical implications, our research has shown that it is possible to identify which pre-cancerous cells develop into myeloid leukaemia in children with Down syndrome by looking at the genomic data.”
Professor Sam Behjati, co-senior author at the Wellcome Sanger Institute and Cambridge University Hospitals and Director of the Cambridge Children’s Hospital Research Institute, said: “Cancer can impact all our lives, and to fully understand all the different subtypes, no matter how rare, we must work together to build our collective knowledge. This international collaboration gives a broader understanding of human cancer, and how different genetic changes must be studied together to gain the full picture of how they interact and cause conditions such as myeloid leukaemia.”
ENDS
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Notes to Editors:
The researchers are incredibly grateful to all of those who participated in this research.
Publication:
M. K. Trinh, K. Schuschel, H. Issa, et al . (2026) ‘Single cell transcriptional evolution of myeloid leukaemia of Down syndrome’. Nature Communications . DOI: 10.1038/s41467-026-71707-2
Funding:
The research was part-funded by Wellcome, the German Research Foundation, and the European Research Council. A full acknowledgement list can be found in the publication.
Selected websites:
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Nature Communications
Single cell transcriptional evolution of myeloid leukaemia of Down syndrome
23-Apr-2026