Aging and Cancer

Mutations raise risk for white blood cell disorder

Some of the first known inherited genetic variants that significantly raise a person’s likelihood of developing clonal hematopoiesis have been identified by researchers at HMS and the Harvard T.H. Chan School of Public Health. This age-related  condition is marked by the accumulation of genetically abnormal white blood cells. Such cells may become cancerous or contribute to inflammation in atherosclerotic plaques, a potent risk factor for heart attacks and strokes.

Amyloid beta plaques (brown) in the cerebral cortex are a hallmark of Alzheimer’s disease.
Amyloid beta plaques (brown) in the cerebral cortex are a hallmark of Alzheimer’s disease.

The researchers note that although clonal hematopoiesis is increasingly seen as an important biomarker of risk for future illness, little has been known about what causes the condition. The study brings new clarity by showing the specific sequence of genetic events that give rise to the abnormal blood cells. It also shows that inherited and acquired mutations are more connected than previously thought.

Acquired mutations are thought to occur randomly over time by either appearing spontaneously or after exposure to damaging agents such as ultraviolet light. Yet the team found examples where inherited variants led to the appearance of specific acquired mutations later in life or gave white blood cells with such mutations a growth advantage over other cells.

Clonal hematopoiesis occurs when a single blood stem cell acquires mutations that cause it to produce more than its share of new cells, including white blood cells. Over time, the mutants outcompete normal blood cells, either by proliferating more rapidly or surviving longer. These genetically dominant blood cells are called clones.

With more research, scientists will be able to better assess the risks each clone confers and use that knowledge to develop environmental or medical interventions that might slow the growth of clones and avert disease.

McCarroll SA, Price AL, et al., Nature, July 2018

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