MYD88 L265P in Waldenström's Macroglobulinemia, IgM Monoclonal Gammopathy, and other B-cell Lymphoproliferative Disorders using Conventional and Quantitative Allele-Specific PCR.

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 Manning, Christina Tripsas, Neal I. Lindeman and Steven P. Treon
This article has an Erratum 121(26):5259

Key points

  • MYD88 L265P is expressed in WM & IgM MGUS patients using AS-PCR assays with potential use in diagnostic discrimination & response assessment


By whole genome and/or Sanger sequencing, we recently identified a somatic mutation (MYD88 L265P) which stimulates NFκB activity, and is present >90% of Waldenstrom’s Macroglobulinemia (WM) patients. MYD88 L265P was absent in 90% of IgM MGUS patients. We therefore developed conventional and real-time allele-specific (AS) PCR assays for more sensitive detection and quantification of MYD88 L265P. Using either assay, MYD88 L265P was detected in 97/104 (93%) WM and 13/24 (54%) IgM MGUS patients, and was either absent or rarely expressed in samples from splenic MZL (2/20; 10%), CLL (1/26; 4%), multiple myeloma (including IgM cases, 0/14), and IgG MGUS (0/9) patients, as well as healthy donors (0/40; p<1.5x10-5 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 bone marrow disease involvement (r=0.89, p=0.008) 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.

  • Submitted September 4, 2012.
  • Accepted December 30, 2012.