Asger Risom
Researchers have identified a molecular pathway involving succinate and the SUCNR1 receptor that may help prevent stem cells from turning cancerous, offering a potential new target for treating aggressive blood cancer.
Researchers say they have uncovered a biological mechanism that could help slow or even block the progression of an aggressive form of blood cancer.
The findings, published in Nature Communications, suggest that controlling specific molecular signals in bone marrow stem cells may influence whether those cells remain healthy or transform into cancer cells — raising hopes for more personalized treatments in the future.
A deadly disease with limited options
The research focuses on acute myeloid leukemia (AML), an aggressive cancer that develops in the bone marrow, where blood cells are produced. While AML can affect people of any age, it is most common in adults over 65. Survival rates remain especially low among older patients, with fewer than 5% surviving long term.
Currently, the only potentially curative treatment is a stem cell transplant — a demanding procedure with significant risks that many elderly patients cannot undergo.
The “accelerator” and the “brake”
In the study, scientists at the University of Oslo examined hematopoietic stem cells — the cells responsible for generating all types of blood cells.
Under normal conditions, these stem cells carefully balance between dormancy and division. If that balance breaks down, abnormal growth can occur, leading to leukemia.
Researchers describe the system as having an “accelerator,” which pushes cells to divide, and a “brake,” which keeps them in a resting state.
The study found that this balance is influenced by a molecule called succinate and its receptor, SUCNR1. Together, they help regulate whether stem cells remain quiescent or begin dividing.
A surprising protective role
Activation of the SUCNR1 receptor appears to help keep stem cells healthy by controlling two proteins linked to cancer progression, S100A8 and S100A9.
The team analyzed patient data and conducted experiments in mice using advanced techniques including RNA sequencing and flow cytometry.
Among patients with AML, lower levels of SUCNR1 were associated with reduced survival. In mouse models, altering levels of succinate, SUCNR1, and S100A9 influenced how the disease developed.
Succinate had previously been viewed primarily as a factor that promotes cancer progression. However, the new findings suggest it may also play a protective role when acting through the SUCNR1 receptor.
Toward personalized treatment
The researchers say the next stage is to determine whether these insights can be translated into clinical therapies.
In the future, measuring SUCNR1 levels could potentially help doctors tailor treatments to a patient’s specific biological profile — offering a more targeted approach to combating acute myeloid leukemia.
Sources: Nature Communications, News.ro
