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Chronic myeloproliferative neoplasms

A highly heterogeneous mutational pattern in POEMS syndrome

Leukemia volume 35, pages 1100–1107 (2021)Cite this article

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Abstract

POEMS syndrome is a rare plasma cell dyscrasia. Little is known about its pathogenesis and genetic features. We analyzed the mutational features of purified bone marrow plasma cells from 42 patients newly diagnosed with POEMS syndrome using a two-step strategy. Whole exome sequencing of ten patients showed a total of 170 somatic mutations in exonic regions and splicing sites, with paired peripheral blood mononuclear cells as a control. Three significantly mutated genes—LILRB1 (10%), HEATR9 (20%), and FMNL2 (10%)—and eight mutated known driver genes (MYD88, NFKB2, CHD4, SH2B3, POLE, STAT3, CHD3, and CUX1) were identified. Target region sequencing of 77 genes were then analyzed to validate the mutations in an additional 32 patients. A total of 32 mutated genes were identified, and genes recurrently mutated in more than three patients included CUX1 (19%), DNAH5 (16%), USH2A (16%), KMT2D (16%), and RYR1 (12%). Driver genes of multiple myeloma (BIRC3, LRP1B, KDM6A, and ATM) and eleven genes reported in light-chain amyloidosis were also identified in target region sequencing. Notably, VEGFA mutations were detected in one patient. Our study revealed heterogeneous genomic profiles of bone marrow plasma cells in POEMS syndrome, which might share some similarity to that of other plasma cell diseases.

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Fig. 1: Fifteen mutated genes with FDR < 1 and eight mutated driver genes were detected in ten patients by WES.
Fig. 2: Gene ontology (GO) and pathway analysis of WES data.
Fig. 3: Likely mutated genes defined by target region sequencing in 32 patients with POEMS syndrome.

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Acknowledgements

Institutional research funding was provided by the National Natural Science Foundation of China (Grant No. 81974011, for Jian Li), Beijing Natural Science Foundation (Grant No. 7182128, for Jian Li), The Capital Health Research and Development of Special Fund (no.2018-2-4015, for Jian Li), The CAMS Innovation Fund for Medical Sciences (Grant No. 2016-12M-1-002, for Jian Li), and The National Key Research and Development Program of China (Grant No. 2016YFC0901503, for Jian Li).

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  1. These authors contributed equally: Jia Chen, Xue-min Gao

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  1. Department of Hematology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Peking Union Medical College, 100730, Beijing, China

    Jia Chen, Xue-min Gao, Hao Zhao, Hao Cai, Lu Zhang, Xin-xin Cao, Dao-bin Zhou & Jian Li

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Chen, J., Gao, Xm., Zhao, H. et al. A highly heterogeneous mutational pattern in POEMS syndrome. Leukemia 35, 1100–1107 (2021). https://doi.org/10.1038/s41375-020-01101-4

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