Scientists have identified a link between cell mutation and bone marrow "aging"

Precancerous changes in blood cells can not only increase the risk of developing leukemia, but also rebuild the bone marrow environment long before the onset of the disease. This conclusion was reached by researchers who studied how mutated cells interact with surrounding tissues. The work shows that not only the mutation itself plays a key role, but also the changes it causes in the bone marrow microenvironment. About how precancerous cells "age" tissues, why it helps them spread, and how the discovery can change the prevention of blood cancer, in the Izvestia article.

Precancerous cells were able to "age" the bone marrow

The study, the results of which are published in the journal Nature Cell Biology, is devoted to clonal hematopoiesis, an age—related condition in which individual hematopoietic stem cells acquire mutations and gradually begin to produce a disproportionately large proportion of blood cells. Clonal hematopoiesis itself is not considered cancer, however, some mutant clones may acquire additional mutations over time and lead to the development of blood cancers.

Previously, it was believed that such cells spread mainly because they gain an advantage over healthy ones. However, a new study has shown that this explanation is not enough. It turned out that mutant cells actively alter the environment of the bone marrow, causing premature aging of mesenchymal stromal cells, cells that support normal hematopoiesis.

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The altered environment helps mutant cells gain an advantage

To understand exactly how this process occurs, the researchers analyzed the activity of individual bone marrow cells in mice and in human tissue samples. It turned out that under the influence of mutant hematopoietic cells, mesenchymal stromal cells enter a state of cellular aging. They cease to perform their functions normally, but they continue to exist and secrete signaling molecules that change the behavior of neighboring cells.

As a result, a microenvironment is formed in which mutant cells gain an additional advantage over healthy ones and expand their clones more easily. The authors of the study compared this process to a weed in a garden.

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A new target for blood cancer prevention

In the next stage of the work, the researchers tested what would happen if senescent stromal cells were removed from the bone marrow. Experiments have shown that after this, the expansion of mutant clones was significantly reduced, and the progression to blood diseases in laboratory animals slowed down. These results indicate that not only the mutation itself plays an important role, but also the environment it forms.

According to the authors, the discovery opens up a new direction in the prevention of blood cancer. Instead of targeting mutant cells exclusively, it may be promising to interfere with bone marrow changes that help these cells spread.

The authors also note that similar mechanisms may exist in other body tissues. Since mutant cell clones occur not only in the blood, but also in the skin, intestines, and esophagus, the researchers plan to test in the future whether environmental change affects the development of other age-related diseases and cancers.