Subclonal evolution in disease progression from MGUS/SMM to multiple myeloma is characterised by clonal stability

Multiple myeloma (MM) is a largely incurable haematological malignancy defined by the clonal proliferation of malignant plasma cells (PCs) within the bone marrow. Clonal heterogeneity has recently been established as a feature in MM, however, the subclonal evolution associated with disease progressi...

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Published inLeukemia Vol. 33; no. 2; pp. 457 - 468
Main Authors Dutta, Ankit K., Fink, J. Lynn, Grady, John P., Morgan, Gareth J., Mullighan, Charles G., To, Luen B., Hewett, Duncan R., Zannettino, Andrew C. W.
Format Journal Article
LanguageEnglish
Published London Nature Publishing Group UK 01.02.2019
Nature Publishing Group
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Summary:Multiple myeloma (MM) is a largely incurable haematological malignancy defined by the clonal proliferation of malignant plasma cells (PCs) within the bone marrow. Clonal heterogeneity has recently been established as a feature in MM, however, the subclonal evolution associated with disease progression has not been described. Here, we performed whole-exome sequencing of serial samples from 10 patients, providing new insights into the progression from monoclonal gammopathy of undetermined significance (MGUS) and smouldering MM (SMM), to symptomatic MM. We confirm that intraclonal genetic heterogeneity is a common feature at diagnosis and that the driving events involved in disease progression are more subtle than previously reported. We reveal that MM evolution is mainly characterised by the phenomenon of clonal stability, where the transformed subclonal PC populations identified at MM are already present in the asymptomatic MGUS/SMM stages. Our findings highlight the possibility that PC extrinsic factors may play a role in subclonal evolution and MGUS/SMM to MM progression.
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ISSN:0887-6924
1476-5551
DOI:10.1038/s41375-018-0206-x