Researchers at University College London (UCL) are investigating why some people with smouldering myeloma (SMM) go on to develop incurable multiple myeloma, while others do not. The project, funded with £209,835 from Cancer Research UK, will examine how inherited genetic differences influence the immune system’s ability to control the disease.
Around 6,500 people are diagnosed with myeloma in the UK each year, and the disease is almost always preceded by earlier conditions including SMM. Although SMM does not generally cause symptoms, around half of patients develop myeloma within five years. Doctors cannot currently reliably predict which patients will progress, creating a challenge around deciding who may benefit from early intervention and who can be safely monitored.
The UCL team will focus on natural killer (NK) cells, which normally recognise and destroy abnormal cells, but have been shown to lose some of their cancer-fighting ability as SMM progresses towards myeloma. Using data from the UK-wide COSMOS study, which includes more than 600 patients with SMM, researchers will investigate whether inherited genetic differences help explain variations in immune responses and disease progression.
The study will examine genes including killer immunoglobulin-like receptors and human leukocyte antigens, which influence how NK cells recognise and respond to abnormal cells. Researchers will also investigate NK cell behaviour within the bone marrow and their ability to attack tumour cells.
Project lead Dr Elise Rees at UCL said the research could help explain differences in disease progression between ethnic groups and support more personalised monitoring and treatment of precancerous conditions.
“The ultimate goal is to uncover why the immune system sometimes fails to stop cancer developing and how this knowledge can be used to intervene earlier,” she said.
People of African ancestry have around twice the risk of developing myeloma, while remaining underrepresented in research. The team hopes that examining genetic and immune differences across populations could help improve understanding of this disparity and identify markers associated with higher progression risk.