Breaking down a protein that myeloma needs to survive

Myeloma is a type of blood cancer that starts in the bone marrow, the soft spongy tissue inside our bones where blood cells are made. Myeloma cells rely on high levels of a specific protein called IRF4 to stay alive. If IRF4 levels drop, myeloma cells usually die. Some treatments work by lowering IRF4 levels indirectly, but over time the cancer can stop responding to these drugs, levels of this protein rise again and the cancer comes back.

Dr Adrain and his team will study a new protein called midnolin, which has the ability to break down IRF4 inside cells. They have found that midnolin exists in two forms. One form is effective at breaking down IRF4, while the other is much weaker. They believe that in myeloma cells, the weaker form is more dominant, which means IRF4 levels stay high and the cancer cells survive.

The team want to develop two new laboratory experiments to understand this. The first experiment will allow them to see how strongly each form of midnolin attaches to IRF4 inside myeloma cells. The second will show which form of midnolin a cell is producing. Together, these tools will help the researchers identify ways to boost the more effective form of midnolin, increasing its ability to break down IRF4 and kill myeloma cells.

If successful, this research could be an important first step towards the development of a new type of treatment for myeloma that works when existing drugs have stopped working. In the longer term, finding ways to directly target IRF4 through midnolin could give people with myeloma a better chance of responding to treatment for longer.