US researchers have unveiled a new genomic scoring system designed to predict the risk of progression to multiple myeloma from pre-cursor conditions.
The “MM-like score” can assess the risk of progression to active cancer and indicate the severity of disease, according to researchers in Boston, Massachusetts, USA. The study also involved European researchers from the UK, Germany, Greece and Italy.
Reporting in Nature Genetics, the researchers say their system adds genetic factors to existing stratification models and involved one of the largest analyses undertaken of whole genome data for myeloma and its precursor conditions. The research involved data from more than 1,000 patients.
The scoring system was validated using 47 samples from 20 patients at various points in the progression of disease. Out of these patients, 13 did not progress and MM-like scores were stable in 11. Of the seven who suffered progression, five had increasing MM-scores.
The researchers say the work also unearthed some surprising finds. This included the observation that the earliest genomic changes linked to the disease may appear as early in life as in their 20s.
The researchers are now developing a ‘liquid biopsy’ test based upon blood samples, instead of bone marrow samples, which they say would make it more accessible and easier to monitor changes over time.
Researcher Dr Gad Getz, of Harvard University, said: “This study greatly improves our ability to discover both potentially clinically actionable cancer-driving mutations in multiple myeloma and the timing of when these events occur across disease states. These insights wouldn’t be possible without access to deeply sequenced whole genomes from a large number of patients and across different disease stages.”
Fellow researcher Dr Irene Ghobrial, director of the centre for early detection of blood cancers at the Dana-Farber Cancer Institute, said: “There has been an urgent need to identify genomic risk factors that predict disease progression in smouldering myeloma.
“This is especially true as we start early therapeutic interception for high risk smouldering multiple myeloma. Our data provides a simple genomic score that can help predict progression and can improve on our clinical markers to help stratify risk for our patients.”
Source:
Alberge JB, Dutta AK, Poletti A, Coorens THH, Lightbody ED, Toenges R, Loinaz X, Wallin S, Dunford A, Priebe O, Dagan J, Boehner CJ, Horowitz E, Su NK, Barr H, Hevenor L, Towle K, Beesam R, Beckwith JB, Perry J, Cordas Dos Santos DM, Bertamini L, Greipp PT, Kübler K, Arndt PF, Terragna C, Zamagni E, Boyle EM, Yong K, Morgan G, Walker BA, Dimopoulos MA, Kastritis E, Hess J, Sklavenitis-Pistofidis R, Stewart C, Getz G, Ghobrial IM. (2025) “Genomic landscape of multiple myeloma and its precursor conditions.” Nature Genetics, 21 May 2025, doi: 10.1038/s41588-025-02196-0.
Link: https://www.nature.com/articles/s41588-025-02196-0
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