MYD88 L265P in Waldenström macroglobulinemia, immunoglobulin M monoclonal gammopathy, and other B-cell lymphoproliferative disorders using conventional and quantitative allele-specific polymerase chain reaction.

Lian Xu, Zachary R. Hunter, Guang Yang, Yangsheng Zhou, Yang Cao, Xia Liu, Enrica Morra, Alessandra Trojani, Antonino Greco, Luca Arcaini, Maria Varettoni, Jennifer R. Brown, Yu Tzu Tai, Kenneth C. Anderson, Nikhil C. Munshi, Christopher J. Patterson, Robert J. Manning, Christina K. Tripsas, Neal I. Lindeman, Steven P. Treon

Research output: Contribution to journalArticle

Abstract

By whole-genome and/or Sanger sequencing, we recently identified a somatic mutation (MYD88 L265P) that stimulates nuclear factor κB activity and is present in >90% of Waldenström macroglobulinemia (WM) patients. MYD88 L265P was absent in 90% of immunoglobulin M (IgM) monoclonal gammopathy of undetermined significance (MGUS) patients. We therefore developed conventional and real-time allele-specific polymerase chain reaction (AS-PCR) assays for more sensitive detection and quantification of MYD88 L265P. Using either assay, MYD88 L265P was detected in 97 of 104 (93%) WM and 13 of 24 (54%) IgM MGUS patients and was either absent or rarely expressed in samples from splenic marginal zone lymphoma (2/20; 10%), CLL (1/26; 4%), multiple myeloma (including IgM cases, 0/14), and immunoglobulin G MGUS (0/9) patients as well as healthy donors (0/40; P <1.5 × 10(-5) for WM vs other cohorts). Real-time AS-PCR identified IgM MGUS patients progressing to WM and showed a high rate of concordance between MYD88 L265P ΔCT and BM disease involvement (r = 0.89, P = .008) in WM patients undergoing treatment. These studies identify MYD88 L265P as a widely present mutation in WM and IgM MGUS patients using highly sensitive and specific AS-PCR assays with potential use in diagnostic discrimination and/or response assessment. The finding of this mutation in many IgM MGUS patients suggests that MYD88 L265P may be an early oncogenic event in WM pathogenesis.

Original languageEnglish
Pages (from-to)2051-2058
Number of pages8
JournalBlood
Volume121
Issue number11
DOIs
Publication statusPublished - Mar 14 2013

ASJC Scopus subject areas

  • Hematology
  • Biochemistry
  • Cell Biology
  • Immunology

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    Xu, L., Hunter, Z. R., Yang, G., Zhou, Y., Cao, Y., Liu, X., Morra, E., Trojani, A., Greco, A., Arcaini, L., Varettoni, M., Brown, J. R., Tai, Y. T., Anderson, K. C., Munshi, N. C., Patterson, C. J., Manning, R. J., Tripsas, C. K., Lindeman, N. I., & Treon, S. P. (2013). MYD88 L265P in Waldenström macroglobulinemia, immunoglobulin M monoclonal gammopathy, and other B-cell lymphoproliferative disorders using conventional and quantitative allele-specific polymerase chain reaction. Blood, 121(11), 2051-2058. https://doi.org/10.1182/blood-2012-09-454355