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Multiple Myeloma Gammopathies

POEMS syndrome remains a mystery after 40 years

Leukemia volume 35, pages 1220–1221 (2021)Cite this article

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The acronym POEMS was coined by Bardwick et al. in 1980 to describe a paraneoplastic syndrome due to an underlying monoclonal gammopathy [1]. Although our understanding of its manifestations, treatment and prognosis has advanced in recent years, the critical genetic events occurring in its plasma cells are not fully elucidated. Chen et al. reported a highly heterogenous mutational profile in 42 POEMS patients [2]. The results were largely concordant with a previous study from Japan; however, significantly discordant findings were also evident [3].

Both studies utilized a two-step approach, whole exome followed by targeted sequencing, to tackle the somatic mutations in bone marrow plasma cells prepared by CD138 magnetic beads sorting. Of the seven recurrently mutated genes identified by Nago et al., five were validated by Chen et al. However, the later study reported a much higher mutation frequency (87.5% vs. 45.0%) as well as unique driver mutations associated with multiple myeloma in POEMS patients. Beside different sample size and sequencing depth mentioned by Chen et al., other possible explanations underlying the discordance also need to be considered, such as patient characteristics. Compared to the newly diagnosed cases with classic λ light chain-restriction in Chen’s study, Nago et al. included relapsed as well as non-λ cases. Of note, only one of the five (20.0%) relapsed patients had a mutation.

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  1. Department of Internal Medicine, University of South Florida, Morsani College of Medicine, Tampa, FL, USA

    Chen Wang

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Correspondence to Chen Wang.

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Wang, C. POEMS syndrome remains a mystery after 40 years. Leukemia 35, 1220–1221 (2021). https://doi.org/10.1038/s41375-021-01168-7

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