Researchers at the University Medical Center Mainz have uncovered how long-lasting inflammation in bone marrow can encourage cancer to develop in people who carry age-related mutations in their blood stem cells.
Blood cancers such as leukemia begin with genetic changes in hematopoietic stem cells, the cells that form all blood components. The Mainz team has now shown that early, chronic inflammation changes the bone-marrow environment in people with these mutations. This altered environment strengthens harmful inflammatory cycles and weakens healthy blood production. Their findings, published in Nature Communications, may support new early-stage treatment approaches for blood cancers.
A Fragile Balance in the Bone Marrow
The bone marrow produces millions of new blood and immune cells every second. This process depends on hematopoietic stem cells, supportive stromal cells, and immune-regulating molecules. Together, they form the bone-marrow microenvironment: a complex system where cells constantly exchange signals. This environment determines how both healthy and mutated cells grow. However, researchers have long lacked clarity on how these surroundings help drive blood cancer.
Inflammation Appears Long Before Symptoms
The international research team, led by Dr. Borhane Guezguez in Mainz and Dr. Judith Zaugg at EMBL Heidelberg, studied people with age-related stem-cell mutations. One common condition is clonal hematopoiesis of indeterminate potential (CHIP). It appears in 10–20% of adults over 60 and nearly 30% over 80. CHIP has no symptoms but raises the risk of blood cancer tenfold and also increases the risk of cardiovascular disease and overall mortality.
Myelodysplastic syndromes (MDS), another age-linked disorder, lead to poor blood production and bone-marrow failure. MDS affects up to 20 in every 100,000 people over age 70. Up to 30% of MDS cases progress to acute myeloid leukemia (AML), a fast-growing and often deadly cancer.
A Self-Reinforcing Inflammatory Loop
In samples from people with CHIP and MDS, the scientists found a distinct population of inflammatory stromal stem cells. These cells had replaced the normal stromal cells in the bone marrow. The inflammatory cells released high levels of signaling molecules. These molecules drew in and activated immune cells that respond to interferon, a natural immune protein. The resulting interferon-responsive T cells intensified inflammation even further. This cycle interfered with normal blood formation and supported the growth of mutated cells.
Path Toward Preventive Therapies
“Our research shows that the bone-marrow microenvironment actively shapes the earliest steps of blood cancer,” says Dr. Guezguez. Genetic tools can now detect cancer-linked mutations years before symptoms appear. These new findings suggest that therapies targeting the bone-marrow environment could slow or stop disease progression in people with CHIP or MDS. The unique molecular signatures of the inflammatory stromal cells and interferon-responsive T cells may also serve as early biomarkers to identify high-risk individuals.
The team notes that the work also deepens scientific understanding of “inflammaging,” a chronic, low-grade inflammation involved in many age-related conditions, including cancer, heart disease, and metabolic disorders.
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