Impact of DNA mutations on blood cell production discovered

0

Researchers have discovered how genetic mutations hijack blood cell production at different times of life and how these changes are linked to the development of age-related diseases, including blood cancer.

A new study shows how DNA mutations impact the production of blood cells. Credit: Karen Arnott/EMBL.

The new study, published in Nature, represents the first time that the lifelong impact of genetic mutations on cell growth dynamics has been explored. The work was led by scientists from the Wellcome Sanger Institute, Cambridge Stem Cell Institute, EMBL European Bioinformatics Institute (EMBL-EBI) and collaborators.

Why do cells have DNA mutations?

All human cells acquire genetic changes in their DNA throughout their lives, called somatic mutations. A specific subset of these mutations cause cells to multiply. This is common in blood stem cells and results in the growth of populations of cells with identical mutations called ‘clones’. This process, called “clonal hematopoiesis,” becomes pervasive with age and is a risk factor for developing blood cancer and other age-related conditions.

Cell and patient tracking

“For the first time, we were able to use genomic analysis to understand the past, present and future of mutant clones in our blood,” said Moritz Gerstung, co-lead author of the study, from the European Institute of Bioinformatics at EMBL and the German Cancer Research Center (DKFZ). “These data show that the dynamics of blood clones are surprisingly predictable over a period of years, but also highlight that they change over a lifetime in ways we don’t yet understand.”

To understand how and when clonal hematopoiesis develops, how it is influenced by aging, and how it relates to disease, the researchers followed nearly 700 blood cell clones from 385 people over the age of 55. Participants gave regular blood samples until age 16.

DNA sequencing of blood samples showed that more than 90% of the clones grew at a stable exponential rate over the period studied. The growth rate was mainly influenced by the nature of the mutated gene in each clone.

Using the past to predict future mutations

“Our findings reveal how acquired genetic DNA alters blood formation over the course of our lifetime, with normal blood stem cells competing with cells with pre-leukemic mutations,” said Margarete Fabre, PhD student at the Wellcome Sanger Institute and the University of Cambridge. “Understanding why certain mutations are prevalent in young people and others in old people could help us find ways to maintain the health and diversity of our blood cells.”

“Our work shows that mutations not only grow at different rates, but also appear at different times in adult life, and that there is a good association between higher growth rates and progression to myeloid cancers.” , concluded Jose Guilherme Coelho Peres de Almeida, previously a PhD student at EMBL-EBI, now a Postdoc at the Center Champalimaud de l’Inconnu. “This not only provides insight into the basic biology of somatic evolution, but may also be clinically useful.”

This is a short version of a press release posted on the Wellcome Sanger Institute website.

Funding

This research was funded by the Leukemia and Lymphoma Society, Rising Tide Foundation for Clinical Cancer Research, Wellcome Trust and Cancer Research UK.

The patients were part of the SardiNIA longitudinal cohort study supported by the National Institute of Health and the European Union’s Horizon 2020 research and innovation program.

/Public release. This material from the original organization/authors may be ad hoc in nature, edited for clarity, style and length. The views and opinions expressed are those of the author or authors.View Full here.
Share.

Comments are closed.