Detection and prevalence of monoclonal gammopathy of undetermined significance: a study utilizing mass spectrometry-based monoclonal immunoglobulin rapid accurate mass measurement
Open accessAbstract
High-sensitivity mass spectrometry assays are available to detect monoclonal immunoglobulins. To better assess the prevalence of monoclonal gammopathy of undetermined significance (MGUS), we identified 300 patients diagnosed with MGUS or related gammopathy who had a prior negative work-up for monoclonal proteins as part of the Olmsted County MGUS screening study. Two mass spectrometry-based detection methods (matrix-assisted laser desorption/ionization-time of flight (MALDI-TOF) and monoclonal immunoglobulin rapid accurate mass measurements (miRAMM) along with traditional immunofixation were performed on the Olmsted baseline and MGUS diagnostics serum samples. Among the 226 patients considered negative for MGUS based on protein electrophoresis and serum-free light-chain assay, a monoclonal protein could be detected at baseline in 24 patients (10.6%) by immunofixation, 113 patients (50%) by MADLI-TOF mass spectrometry, and 149 patients (65.9%) by miRAMM mass spectrometry. In addition, using miRAMM, some patients demonstrated an oligoclonal to monoclonal transition giving insight into the origin of MGUS. Using the sensitive miRAMM, MGUS is present in 887 of 17,367 persons from the Olmsted County cohort, translating into a prevalence of 5.1% among persons 50 years of age and older. This represents the most accurate prevalence estimate of MGUS thus far.
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All cases of multiple myeloma are preceded by precursor conditions such as smoldering multiple myeloma and monoclonal gammopathy of undetermined significance, often decades before diagnosis.
“MM is well-described to be universally preceded by precursor states, often decades before it is even diagnosed.”
From Evolution of Multiple Myeloma from a Genomic Perspective (2026) · cites this paper as [14]
The Results (Patient cohort; page not provided) state that MGUS always precedes multiple myeloma, supporting the universal-precursor part of the claim. The Discussion (page not provided) says MGUS may be present undetected for a median of more than 10 years before MGUS is clinically recognized, but it does not establish that myeloma is often preceded by precursor states decades before myeloma diagnosis. The supplied passages also do not address smoldering multiple myeloma. (LLM, conf=0.87)
Experimental — accuracy not yet measuredMass spectrometry studies show that the percentage of MGUS/SMM is higher than previously reported.
“The use of mass spectrometry has allowed independent groups to show that the percentage of MGUS/SMM is higher than previously reported.14,36”
From Evolution of Multiple Myeloma from a Genomic Perspective (2026) · cites this paper as [14]
The Results (‘Prevalence of MGUS’) report a 5.1% MGUS prevalence using miRAMM, versus 3.5% using the conventional screening method, supporting the claim for MGUS in people over 50. The cited paper does not establish a higher prevalence of SMM or, by itself, a finding by independent groups. (LLM, conf=0.88)
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Cites
Prevalence of monoclonal gammopathy of undetermined significance
Kyle, R. A., Therneau, T. M., Rajkumar, S. V., Larson, D. R., Plevak, M. F., Offord, J. R., Dispenzieri, A., Katzmann, J. A., & Melton, L. J. (2006) · New England Journal of Medicine · doi:10.1056/nejmoa054494 · Cited by 1,423 · see citing works
Self-citationLong-Term Follow-up of Monoclonal Gammopathy of Undetermined Significance
Kyle, R. A., Larson, D. R., Therneau, T. M., Dispenzieri, A., Kumar, S., Cerhan, J. R., & Rajkumar, S. V. (2018) · New England Journal of Medicine · doi:10.1056/nejmoa1709974 · Cited by 647 · see citing works
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Research works printed but not linked: 10
- [2]Dispenzieri A Prevalence and risk of progression of light-chain monoclonal gammopathy of undetermined significance: a retrospective population-based cohort study Lancet 2010 375 1721 1728 10.1016/S0140-6736(10)60482-5 20472173 PMC2904571 · DOI
- [3]Landgren O Racial disparities in the prevalence of monoclonal gammopathies: a population-based study of 12 482 persons from the national health and nutritional examination survey Leukemia 2014 28 1537 1542 10.1038/leu.2014.34 24441287 PMC4090286 · DOI
- [4]Kyle RA A long-term study of prognosis of monoclonal gammopathy of undetermined significance N. Engl. J. Med. 2002 346 564 569 10.1056/NEJMoa01133202 11856795 · DOI · Paper page
- [6]Landgren O Graubard B I Kumar S Kyle R A Katzmann J A Murata K Costello R Dispenzieri A Caporaso N Mailankody S Korde N Hultcrantz M Therneau T M Larson D R Cerhan J R Rajkumar S V Prevalence of myeloma precursor state monoclonal gammopathy of undetermined significance in 12372 individuals 10–49 years old: a population-based study from the National Health and Nutrition Examination Survey Blood Cancer Journal 2017 7 10 e618 e618 10.1038/bcj.2017.97 29053158 PMC5678222 · DOI
- [7]Therneau TM Incidence of monoclonal gammopathy of undetermined significance and estimation of duration before first clinical recognition Mayo Clinic Proc. 2012 87 1071 1079 10.1016/j.mayocp.2012.06.014 PMC3541934 22883742 · DOI
- [8]Mills JR Comprehensive assessment of M-proteins using nanobody enrichment coupled to MALDI-TOF mass spectrometry Clin. Chem. 2016 62 1334 1344 10.1373/clinchem.2015.253740 27540026 · DOI
- [9]Barnidge DR Using mass spectrometry to monitor monoclonal immunoglobulins in patients with a monoclonal gammopathy J. Proteome Res. 2014 13 1419 1427 10.1021/pr400985k 24467232 · DOI
- [10]Milani P The utility of MASS-FIX to detect and monitor monoclonal proteins in the clinic Am. J. Hematol. 2017 92 772 779 10.1002/ajh.24772 28439985 · DOI
- [11]Botz CM Barnidge DR Murray DL Katzmann JA Detecting monoclonal light chains in urine: microLC-ESI-Q-TOF mass spectrometry compared to immunofixation electrophoresis Br. J. Haematol. 2014 167 437 438 10.1111/bjh.13003 25039602 · DOI
- [13]Mills JR Barnidge DR Dispenzieri A Murray DL High sensitivity blood-based M-protein detection in sCR patients with multiple myeloma Blood Cancer J. 2017 7 e590 10.1038/bcj.2017.75 28841203 PMC5596386 · DOI
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Multiple myeloma: 2024 update on diagnosis, risk-stratification, and management
Rajkumar, S. V. (2024) · American Journal of Hematology · doi:10.1002/ajh.27422 · Cited by 534 · see citing works
Self-citationDutta, A. K., Alberge, J.-B., Lightbody, E. D., Boehner, C. J., Dunford, A., Sklavenitis-Pistofidis, R., Mouhieddine, T. H., Cowan, A. N., Su, N. K., Horowitz, E. M., et al. (2023) · Cancer Discovery · doi:10.1158/2159-8290.cd-22-0482 · Cited by 41 · see citing works
Temporal genomic dynamics shape clinical trajectory in multiple myeloma
Maura, F., Kaddoura, M., Poos, A. M., Baughn, L. B., Ziccheddu, B., Bärtsch, M.-A., Cirrincione, A., Maclachlan, K., Chojnacka, M., Diamond, B., et al. (2025) · Nature Genetics · doi:10.1038/s41588-025-02292-1 · Cited by 14 · see citing works
Self-citationEvolution of Multiple Myeloma from a Genomic Perspective
Maura, F., Samur, M., & Munshi, N. (2026) · Blood · doi:10.1182/blood.2024026313 · Cited by 8 · see citing works
- Authors
- Murray, D., Kumar, S. K., Kyle, R. A., Dispenzieri, A., Dasari, S., Larson, D. R., Vachon, C., Cerhan, J. R., & Rajkumar, S. V.
- Affiliations
- Mayo Clinic (US)
- Corresponding author
- Murray, David
- ORCID
- Venue
- Blood Cancer Journal
- Published
- 2019-12-13
- Volume
- 9
- Issue
- 12
- Pages
- 102-102
- ISSN
- 2044-5385 (ISSN-L)
- PMC
- PMC6910906
- OpenAlex
- W2996405388
- Cited by
- 102
- References
- 2
- Citations by year
- 2026: 16 · 2025: 17 · 2024: 14 · 2023: 13 · 2022: 18 · 2021: 16 · 2020: 8
- FWCI
- 7.41
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- Blood Cancer Journal (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
- Funders
- U.S. Department of Health & Human Services | NIH | National Cancer Institute (CA 107476, CA 168762, CA186781)
- Topics
- Health Sciences › Medicine › Hematology › Multiple Myeloma Research and Treatments
- Health Sciences › Medicine › Genetics › Chronic Lymphocytic Leukemia Research
- Physical Sciences › Chemistry › Spectroscopy › Mass Spectrometry Techniques and Applications
- Keywords
- monoclonal gammopathy of undetermined significance, M protein, MALDI-TOF mass spectrometry, immunofixation, free light chains, prevalence
- MeSH terms
- Adolescent, Aged, Aged, 80 and over, Child, Child, Preschool, Diagnosis, Differential, Female, Humans, Immunoglobulin Light Chains, Infant, Male, Middle Aged, Monoclonal Gammopathy of Undetermined Significance, Myeloma Proteins, Paraproteinemias, Mass Spectrometry, Biomarkers, Tumor, Prevalence, Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
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