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As people age, their bodies change in many ways. Some changes are visible, others are hidden. One hidden change is clonal hematopoiesis (CH). This happens when blood stem cells in the bone marrow develop genetic mutations.
Mutated cells produce groups of blood cells that differ genetically from healthy cells. CH itself is not cancer. However, it increases the risk of blood cancers, such as leukemia, later in life.
Why TP53 Mutations Are Risky
A study by Northwestern Medicine, published in the Journal of Clinical Investigation, explored why mutations in the TP53 gene raise leukemia risk.
Many people with CH never develop cancer. But those with TP53 mutations are more likely to progress to leukemia. Researchers wanted to understand why mutated cells grow faster than healthy ones.
Inflammation Gives Mutated Cells an Advantage
Using mice with similar mutations, researchers found that inflammatory stress helps mutated cells. Inflammation can come from infections or other immune triggers.
Healthy cells weaken under inflammation. Mutated cells resist damage and grow faster. This gives them an advantage over healthy cells.
The Role of the NLRP1 Inflammasome
The study identified a key factor: the NLRP1 inflammasome, part of the immune system. It acts as an internal alarm.
In people with TP53 mutations, this alarm increases inflammation. Ironically, the inflammation helps mutated cells grow while harming healthy ones. Chronic inflammation naturally rises with age, which makes the problem worse.
Mutations Keep Inflammation Going
TP53 mutations also change how cells process RNA. This keeps inflammation active in the bone marrow. Over time, it supports the growth of mutated cells and raises cancer risk.
Blocking Inflammation Could Prevent Cancer
The researchers found that blocking the inflammatory signal IL-1B removes the advantage of mutated cells.
This discovery opens the door to preventive treatments. Such treatments could stop blood cancers before they develop in high-risk individuals.
Conclusion
This study shows how aging, genetics, and inflammation interact to raise leukemia risk. It also suggests ways to help older adults with TP53 mutations stay healthier. Targeting inflammation may prevent blood cancers before they start.
