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Detection of the MYD88L265P and CXCR4S338X mutations by cell-free DNA in Waldenström macroglobulinemia

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Abstract

We aimed to detect the MYD88L265P and CXCR4S338X mutations in cell-free DNA (cfDNA) in patients with Waldenström macroglobulinemia (WM). We collected peripheral blood and paired bone marrow aspirates from 27 WM patients (including 16 patients with newly diagnosed WM, 3 patients with WM in relapse and 8 patients with WM during treatment). cfDNA was extracted from peripheral blood using a QIAamp Circulating Nucleic Acid Kit. The MYD88L265P and CXCR4S338X mutations were detected by real-time allele-specific PCR (AS-PCR) in cfDNA and genomic DNA (gDNA) extracted from bone marrow aspirates. The sensitivity of real-time AS-PCR for detecting MYD88L265P in cfDNA was determined using a serial dilution of 10%, 2%, 0.4% and 0.08% MYD88L265P cfDNA in wild-type cfDNA. Among the 27 patients, MYD88L265P was detected in 88.9% of them in gDNA and in 85.2% of them in cfDNA, with a concordance rate of 96.3%. The concordance rates were 93.8%, 100% and 100% in patients with newly diagnosed WM, patients with WM in relapse and patients with WM during treatment, respectively. The sensitivity of real-time AS-PCR for detecting MYD88L265P in cfDNA was 0.4%. CXCR4S338X was detected in 6.3% of the 16 newly diagnosed WM patients in both gDNA and cfDNA, with a concordance rate of 100.0%. It is feasible to apply cfDNA to detect MYD88L265P and CXCR4S338X in WM patients with a high concordance rate.

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Acknowledgments

The authors would like to thank all the patients and their families who participated in this study.

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  1. Yan-Yan Wu and Ming-Nan Jia contributed equally to this work.

Authors and Affiliations

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

    Yan-Yan Wu, Ming-Nan Jia, Hao Cai, Yu Qiu, Dao-Bin Zhou, Jian Li & Xin-Xin Cao

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Contributions

Y.Y.W. and M.N.J. were the main researchers and contributed to writing this manuscript. Y.Q. and H.C. helped collecting blood and bone marrow samples and did the technical work. D.B.Z., J.L. and X.X.C. planned the study and revised the manuscript. All authors agree that this manuscript can be published in the Journal of Annals of Hematology.

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Correspondence to Xin-Xin Cao.

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This study was performed in accordance with the ethical standards of the Institutional Ethics Committee of Peking Union Medical College Hospital at the Chinese Academy of Medical Sciences & Peking Union Medical College and with the 1964 Declaration of Helsinki and its later amendments or comparable ethical standards.

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Written or verbal informed consent was obtained from all individual participants included in the study.

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Wu, YY., Jia, MN., Cai, H. et al. Detection of the MYD88L265P and CXCR4S338X mutations by cell-free DNA in Waldenström macroglobulinemia. Ann Hematol 99, 1763–1769 (2020). https://doi.org/10.1007/s00277-020-04139-7

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