Acute myeloid leukaemia (AML) is an aggressive form of blood cancer. It affects people of all ages but is most common in those over 65. Around 150 people are diagnosed with the disease each year in Norway. Men are affected slightly more often than women. Fewer than 5 in 100 patients over the age of 65 survive.
This type of leukaemia arises in the bone marrow, where blood cells are produced. The only treatment that can cure the disease is stem cell transplantation, which is highly intensive and therefore not available to everyone, including elderly patients, due to its severe potential side effects.
In a new study, researchers have examined how cancer cells develop in the bone marrow and whether it might be possible to stop them.
"Our study provides new insights into acute myeloid leukaemia. We believe the findings can be used to develop new treatments for the disease in the future," says Associate Professor Lorena Arranz at the University of Oslo. She is also Leader of the group Stem Cells, Ageing and Cancer, and Deputy Director at the Centre for Embryology and Healthy Development, CRESCO. Together with her team, she aims to find better ways to detect and treat leukaemia.
The study is published in Nature Communications.
Can we prevent stem cells from becoming cancer cells?
In the study, the researchers focused on blood stem cells in the bone marrow. One of the unique features of stem cells is that they can become many different types of cells. Blood stem cells can develop into all types of blood cells.
"Stem cells have the fascinating abilities to renew and develop into mature cells throughout life. This happens through cell division and differentiation. Both processes must be tightly controlled, because if they become imbalanced, cells can turn into cancer cells," she explains.
Stem cells can either lie dormant or divide actively and become new blood cells. In healthy individuals, they develop into red blood cells, white blood cells and platelets. In people with acute blood cancer, by contrast, stem cells develop into cancer cells rather than healthy blood cells.
What if we could prevent this from happening? Arranz and her colleagues believe it may be possible.
Signals tell the stem cell what to do
How stem cells develop depends on signals from their surrounding environment.
"We have identified signals that influence the development of this type of leukaemia and that we can exploit to fight the cancer," she says.
The body must constantly ensure that it produces enough blood while also preserving stem cells for later in life. The signals the researchers identified help maintain a healthy balance by telling the stem cell whether to remain dormant or become a new cell.
"The system has both an accelerator and a brake. The accelerator tells the stem cell to divide and make more cells, while the brake tells the stem cell to stay put," Arranz explains.
The researchers have found that these signals involve the molecules succinate and succinate receptor SUCNR1. Their levels influence whether the stem cells press the accelerator or apply the brake. SUCNR1 activation keeps stem cells healthy by controlling two cancer promoter proteins, S100A8 and S100A9.
Influencing the development of blood cancer in mice
In the study, the researchers examined data from patients with acute myeloid leukaemia. They also conducted experiments in mice with this type of blood cancer, using advanced methods such as stem cell analyses, RNA sequencing and spectral flow cytometry.
In patients, they studied the levels of expression of SUCNR1.
"We found that low levels of SUCNR1 in patients are associated with poorer survival," says Arranz.
They also observed that the levels of these molecules and the associated signalling through S100A8 and S100A9 influenced how the disease progressed in mice.
"In short, we showed that we could influence the development of leukaemia in mice by altering the levels of succinate, SUCNR1 and S100A9," the associate professor says.
Potential for a new treatment for acute myeloid leukaemia
Arranz is optimistic about the way ahead.
"Succinate has typically been seen as a 'bad guy' that drives the progression and worsening of this form of blood cancer. We have now discovered a new, protective side to succinate, acting on SUCNR1," she says.
"The next step will be to explore how we can harness this in treatment."
Researcher Vincent Cuminetti in her team at CRESCO has played a central role in the study. He, too, sees strong potential for future new treatments for blood cancer.
"We believe the study can help develop better personalised treatments for patients based on SUCNR1 levels in the future," says Vincent Cuminetti.
Reference
Cuminetti, V., Boet, E., Heugel, M., Konieczny, J., Bernal, A., Gomez, M. J., ... & Arranz, L. (2026). Succinate receptor 1 restricts hematopoiesis and prevents acute myeloid leukemia progression. Nature Communications. You can access the article here.
