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Multiple myeloma gammopathies

N-glycosylation of monoclonal light chains on routine MASS-FIX testing is a risk factor for MGUS progression

Leukemia volume 34, pages 2749–2753 (2020)Cite this article

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Abstract

Our group previously demonstrated that M-protein light chain (LC) glycosylation can be detected on routine MASS-FIX testing. Glycosylation is increased in patients with immunoglobulin LC amyloidosis (AL) and rarely changes over the course of a patient’s lifetime. To determine the rates of progression to AL and other plasma cell disorders (PCDs), we used residual serum samples from the Olmsted monoclonal gammopathy of undetermined significance (MGUS) screening cohort. Four-hundred and fourteen patients with known MGUS were tested by MASS-FIX, and 25 (6%) were found to have glycosylated LCs. With a median follow-up of surviving patients of 22.2 years, the 20-year progression rates to a malignant PCD were 67% (95% CI 29%, 84%) and 13% (95% CI 9%, 18%) for patients with and without glycosylated LCs, respectively. The risk of progression was independent of Mayo MGUS risk score. The respective rates of progression to AL at 20 years were 21% (95% CI 0.0%, 38%) and 3% (95% CI 0.6%, 5.5%). In summary, monoclonal LC glycosylation is a potent risk factor for progression to AL, myeloma, and other PCDs, an observation which could lead to earlier diagnoses and potentially reduced morbidity and mortality.

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Fig. 1: Rates of progression based on N-glycosylation status of the monoclonal light chains.

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Acknowledgements

This research was supported by Mayo Clinic, Rochester, MN, US NIH CA186781, The Predolin Foundation, The JABBS Foundation.

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Authors and Affiliations

  1. Division of Hematology, Mayo Clinic, Rochester, MN, USA

    Angela Dispenzieri, S. V. Rajkumar, R. A. Kyle, S. K. Kumar & Taxiarchis Kourelis

  2. Department of Laboratory Medicine, Mayo Clinic, Rochester, MN, USA

    Angela Dispenzieri, Bonnie Arendt, Maria Willrcih & David Murray

  3. Department of Health Sciences Research, Mayo Clinic, Rochester, MN, USA

    D. R. Larson & Surendra Dasari

Authors
  1. Angela Dispenzieri
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  2. D. R. Larson
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  4. R. A. Kyle
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Contributions

AD and DM designed the study. AD and DRL analyzed, interpreted the data, and edited the manuscript. BA performed the LC-MS experiments. Other authors contributed intellectual content and review of this manuscript.

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Correspondence to Angela Dispenzieri.

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DM and SD have intellectual property rights to the MASS-FIX assay and patents. The other authors have no conflicts related to this work.

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Dispenzieri, A., Larson, D.R., Rajkumar, S.V. et al. N-glycosylation of monoclonal light chains on routine MASS-FIX testing is a risk factor for MGUS progression. Leukemia 34, 2749–2753 (2020). https://doi.org/10.1038/s41375-020-0940-8

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