Scientists have discovered a rare genetic variant that slows the growth of mutated blood-forming stem cells and thereby reduces the risk of developing leukemia, reports News Medical Life Sciences.

This discovery helps explain why some people are naturally more resistant to clonal cell expansion and age-related blood disorders, even despite the accumulation of potentially dangerous mutations.

As people age, body tissues quietly accumulate numerous genetic changes, some of which can contribute to cancer development. In the blood-forming system, such mutations are often detected in otherwise healthy individuals in the form of clonal hematopoiesis—a condition in which certain clones of blood stem cells gain a growth advantage and gradually outcompete normal cells. This condition, also known as clonal hematopoiesis of indeterminate potential (CHIP), is associated with an increased risk of blood cancers as well as chronic diseases, including cardiovascular conditions. However, not all carriers of these mutations go on to develop disease, and in some cases mutated clones remain stable over time or even shrink, pointing to the existence of restraining factors.

To identify such protective mechanisms, Gaurav Agarwal and his colleagues conducted a large-scale genetic analysis involving more than 640,000 people. The researchers identified a regulatory DNA variant that does not directly code for proteins but significantly reduces the risk of clonal hematopoiesis and lowers the likelihood of developing blood cancer. The protective effect was linked to reduced activity of the MSI2 gene, which plays a key role in maintaining stem cells.

Experiments using genetically modified human stem cells showed that this variant disrupts the binding of an important transcription factor, GATA2, thereby lowering MSI2 expression levels. As a result, an entire network of genes—on which mutated cells depend for competitive growth—is suppressed.

Notably, the same genetic network is particularly active in cells carrying high-risk oncogenic mutations and in children with acute myeloid leukemia, where its heightened activity is associated with poorer survival outcomes.