Genetic changes that affect the risk of developing pre-leukaemia identified 

New genetic variants have been identified that increase the likelihood of developing clonal haematopoiesis, which is a risk factor for multiple diseases including blood cancer

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14 inherited genetic variants have been identified which significantly increase the risk of a person developing a blood disorder that is associated with the onset of some types of cancer and heart disease.

The new research, led by scientists from the Wellcome Sanger Institute, the Universities of Bristol and Cambridge, the Health Research Institute of Asturias in Spain, and AstraZeneca, discovered multiple inherited genetic variants that increase the likelihood of developing clonal haematopoiesis, which is a risk factor for multiple diseases including blood cancer.

The study, published 14 July 2022 in Nature Genetics is one of the largest of its kind, analysing data from 421,738 people, and could pave the way for potential new approaches for the prevention and early detection of cancers including leukaemia.

All human cells acquire genetic changes in their DNA throughout life, known as somatic mutations, with a specific subset of somatic mutations driving cells to multiply. This is particularly common in blood-making cells, known as blood stem cells, and results in the growth of populations of cells with identical mutations known as ‘clones’.

Clonal haematopoiesis is a condition characterised by the development of expanding clones of multiplying blood cells in the body, driven by mutations in their DNA.1

Although symptomless, the disorder becomes ubiquitous with age and is a risk factor for developing blood cancer and other age-related diseases.1

Using data from the UK Biobank, a large-scale biomedical database and research resource containing genetic and health information from half a million UK participants, the team were able to show how genetic mutations relate to blood cancers and tumours that develop elsewhere in the body such as lung, prostate, and ovarian cancer.

The team found that clonal haematopoiesis accelerated the process of biological ageing and influenced the risk of developing atrial fibrillation, a condition marked by irregular heartbeats.

The findings also clearly established that smoking is one of the strongest modifiable risk factors for developing the disorder, emphasising the importance of reducing tobacco use to prevent the condition’s onset and its harmful consequences.

“Our findings implicate genes and the mechanisms involved in the expansion of aberrant blood cell clones and can help guide treatment advances to avert or delay the health consequences of clonal haematopoiesis such as progression to cancer and the development of other diseases of ageing.”

Dr Siddhartha Kar, co-lead author, and UKRI Future Leaders Fellow at the University of Bristol from Bristol’s MRC Integrative Epidemiology Unit (IEU)

 “Our study reveals that the cellular mechanisms driving clonal haematopoiesis can differ depending on the mutated gene responsible. This is a challenge as we have many leads to follow, but also an opportunity as we may be able to develop treatments specific to each of the main subtypes of this common phenomenon.”

Professor George Vassiliou, co- lead author, previously at the Wellcome Sanger Institute and now Professor of Haematological Medicine at the University of Cambridge

“We were particularly pleased to see that some of the genetic pathways driving clonal haematopoiesis appear to be susceptible to pharmacological manipulation and represent prioritised targets for the development of new treatments.”

Dr Pedro M. Quiros, co-lead author formerly from the Wellcome Sanger Institute and the University of Cambridge, and now Group Leader at the Health Research Institute of Asturias (Spain)

More information

  1. Jaiswal, B. Ebert. (2019) Clonal hematopoiesis in human aging and disease. Science. DOI: 10.1126/science.aan4673

Further information

Clonal haematopoiesis is the development of mutations in genes involved in blood cell production.  It is diagnosed when a test on a person’s blood or bone marrow sample shows that blood cells are carrying one of the genetic mutations associated with the condition. Clonal haematopoiesis becomes increasingly common with age, affecting more than one in every ten individuals older than 60 years.


Kar SP, et al. (2022) ‘Genome-wide analyses of 200,453 individuals yield new insights into the causes and consequences of clonal hematopoiesis’. Nature Genetics. DOI: 10.1038/s41588-022-01121-z


The study was funded by UK Research and Innovation (UKRI), Cancer Research UK (CRUK), Wellcome, the Royal Society, the Carlos III Health Institute, the Leukaemia and Lymphoma Society, and the Rising Tide Foundation for Clinical Cancer Research.