DALL-E

Novel Genetic Drivers of Aging and Blood Cancer Risk Discovered

Scientists have identified 17 new genes that drive the abnormal overgrowth of mutated blood cells, providing fresh insights into the genetic factors behind aging and blood cancer risks
Engineered Human Therapies
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May 14, 2024

In a groundbreaking discovery, scientists have identified 17 additional genes that drive the abnormal overgrowth of mutated blood cells as we age. Published today (14 May) in Nature Genetics, this research sheds new light on the genetic underpinnings of clonal hematopoiesis—a process linked to aging and associated with increased risks of blood cancers.

The research team, a collaboration between the Wellcome Sanger Institute, Calico Life Sciences, and the University of Cambridge, meticulously analyzed sequencing data from over 200,000 individuals in the UK Biobank cohort. Their collective aim was to identify genes exhibiting signs of 'positive selection,' where mutations enable specific cell populations to expand significantly over time.

These 17 newly discovered genes have similar disease associations to previously known clonal hematopoiesis mutations, underscoring their importance in driving the accumulation of mutant blood cell clones. "While existing genetic tests have been valuable for early disease detection, our findings suggest there are opportunities to improve them further," said Dr. Michael Spencer Chapman, co-first author of the study at the Wellcome Sanger Institute. "By incorporating these 17 additional genes linked to clonal hematopoiesis, we can enhance genetic testing methods to better identify risks of associated blood cancers and cardiovascular diseases."

This discovery opens new avenues for studying the molecular mechanisms underlying clonal hematopoiesis and its role in disease development. It also holds promise for promoting healthier aging and could lead to better genetic tests to identify risks of blood cancers and cardiovascular diseases. As Dr. Jyoti Nangalia, senior author of the study, noted, “Our study reveals a much broader set of genes fuelling mutant blood cell clone accumulation with age, but this is only the beginning. Larger studies across diverse populations are needed to identify remaining driver genes and provide further insights into this process and disease links.”

As we age, our cells amass random genetic mutations. Some of these mutations confer cells a competitive growth advantage, enabling mutant cells to proliferate and surpass healthy cells, forming large clones. When this positive selection occurs in blood stem cells, it is termed clonal hematopoiesis, a process associated with blood cancers, cardiovascular disease, and other age-related ailments.

Previous studies have identified around 70 genes linked to clonal hematopoiesis. However, many recent cases did not involve mutations in any of these known genes, suggesting other genetic factors at play. Researchers set out to map patterns of positive selection in the aging blood system, leveraging whole exome sequencing data from the UK Biobank cohort. They identified 17 genes driving the accumulation of mutant cell clones beyond the known set of drivers.

Incorporating mutations in these newly identified genes increased the prevalence of clonal hematopoiesis by 18 percent in the UK Biobank cohort. "With our newly identified genes, we now have a more complete picture to explore strategies for delaying or reversing abnormal mutant cell overgrowths in blood to promote healthier aging," said Nick Bernstein, co-first author of the study, formerly at Calico Life Sciences and now at NewLimit. "These genes seem to affect inflammation and immunity, important factors in conditions like heart disease and strokes. While interventions based on this research are still a long way off, it opens up possibilities for future treatments across a wide range of diseases."

This study marks a significant step forward in understanding the genetic landscape of clonal hematopoiesis, paving the way for improved diagnostic and therapeutic approaches to combat age-related diseases.

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Novel Genetic Drivers of Aging and Blood Cancer Risk Discovered

by
May 14, 2024
DALL-E

Novel Genetic Drivers of Aging and Blood Cancer Risk Discovered

Scientists have identified 17 new genes that drive the abnormal overgrowth of mutated blood cells, providing fresh insights into the genetic factors behind aging and blood cancer risks
by
May 14, 2024
DALL-E

In a groundbreaking discovery, scientists have identified 17 additional genes that drive the abnormal overgrowth of mutated blood cells as we age. Published today (14 May) in Nature Genetics, this research sheds new light on the genetic underpinnings of clonal hematopoiesis—a process linked to aging and associated with increased risks of blood cancers.

The research team, a collaboration between the Wellcome Sanger Institute, Calico Life Sciences, and the University of Cambridge, meticulously analyzed sequencing data from over 200,000 individuals in the UK Biobank cohort. Their collective aim was to identify genes exhibiting signs of 'positive selection,' where mutations enable specific cell populations to expand significantly over time.

These 17 newly discovered genes have similar disease associations to previously known clonal hematopoiesis mutations, underscoring their importance in driving the accumulation of mutant blood cell clones. "While existing genetic tests have been valuable for early disease detection, our findings suggest there are opportunities to improve them further," said Dr. Michael Spencer Chapman, co-first author of the study at the Wellcome Sanger Institute. "By incorporating these 17 additional genes linked to clonal hematopoiesis, we can enhance genetic testing methods to better identify risks of associated blood cancers and cardiovascular diseases."

This discovery opens new avenues for studying the molecular mechanisms underlying clonal hematopoiesis and its role in disease development. It also holds promise for promoting healthier aging and could lead to better genetic tests to identify risks of blood cancers and cardiovascular diseases. As Dr. Jyoti Nangalia, senior author of the study, noted, “Our study reveals a much broader set of genes fuelling mutant blood cell clone accumulation with age, but this is only the beginning. Larger studies across diverse populations are needed to identify remaining driver genes and provide further insights into this process and disease links.”

As we age, our cells amass random genetic mutations. Some of these mutations confer cells a competitive growth advantage, enabling mutant cells to proliferate and surpass healthy cells, forming large clones. When this positive selection occurs in blood stem cells, it is termed clonal hematopoiesis, a process associated with blood cancers, cardiovascular disease, and other age-related ailments.

Previous studies have identified around 70 genes linked to clonal hematopoiesis. However, many recent cases did not involve mutations in any of these known genes, suggesting other genetic factors at play. Researchers set out to map patterns of positive selection in the aging blood system, leveraging whole exome sequencing data from the UK Biobank cohort. They identified 17 genes driving the accumulation of mutant cell clones beyond the known set of drivers.

Incorporating mutations in these newly identified genes increased the prevalence of clonal hematopoiesis by 18 percent in the UK Biobank cohort. "With our newly identified genes, we now have a more complete picture to explore strategies for delaying or reversing abnormal mutant cell overgrowths in blood to promote healthier aging," said Nick Bernstein, co-first author of the study, formerly at Calico Life Sciences and now at NewLimit. "These genes seem to affect inflammation and immunity, important factors in conditions like heart disease and strokes. While interventions based on this research are still a long way off, it opens up possibilities for future treatments across a wide range of diseases."

This study marks a significant step forward in understanding the genetic landscape of clonal hematopoiesis, paving the way for improved diagnostic and therapeutic approaches to combat age-related diseases.

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