In a new study published in Nature Communications, a research team at the University of Oslo have examined how cancer cells develop in the bone marrow and whether it might be possible to stop them. The study finds a way to stop malignant stem cells. The researchers believe their findings could open up new avenues for treatment in the future.

“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 demonstrates that it is possible to influence the development of leukaemia in mouse models
In the study, the researchers focused on blood stem cells in the bone marrow. 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.

Arranz and her team believe it may be possible to prevent this from happening. 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 signals the researchers identified help maintain a healthy balance by telling the stem cell whether to remain dormant or become a new cell. 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 in a healthy state by controlling the alarmins, S100A8 and S100A9.

In the study, the researchers examined data from patients with acute myeloid leukaemia. They also conducted experiments in mouse models of 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. The study demonstrates that low levels of SUCNR1 in patients are associated with poorer survival. The researchers also observed that the levels of these molecules and the associated signaling through S100A8 and S100A9 influenced how the disease progressed in mouse models. Arranz and her team showed that they could influence the development of leukaemia in mice by altering the levels of succinate, SUCNR1 and S100A9.

Researchers see 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. The next step will be to explore how we can harness this in treatment,” she says. Researcher and first author Vincent Cuminetti also sees potential for future new treatments for blood cancer. “We believe the study can help develop better, future, personalised treatments for patients based on SUCNR1 levels,” says Cuminetti.