Blood Journal
Leading the way in experimental and clinical research in hematology

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

  1. Lian Xu1,
  2. Zachary R. Hunter2,
  3. Guang Yang1,
  4. Yangsheng Zhou1,
  5. Yang Cao1,
  6. Xia Liu1,
  7. Enrica Morra3,
  8. Alessandra Trojani3,
  9. Antonino Greco3,
  10. Luca Arcaini4,
  11. Maria Varettoni4,
  12. Jennifer R. Brown5,
  13. Yu-Tzu Tai6,
  14. Kenneth C. Anderson6,
  15. Nikhil C. Munshi6,
  16. Christopher J. Patterson1,
  17. Robert Manning1,
  18. Christina Tripsas1,
  19. Neal I. Lindeman7, and
  20. Steven P. Treon1,*
  1. 1 Bing Center for Waldenstrom's Macroglobulinemia, Dana-Farber Cancer Institute, Boston, MA, United States;
  2. 2 Department of Medicine, Harvard Medical School, Boston, MA, United States;
  3. 3 Division of Hematology, Niguarda Ca' Granda Hospital, Milan, Italy;
  4. 4 Department of Hematology Oncology, University of Pavia Medical School and Fondazione IRCCS Policlinico San Matteo, Pavia, Italy;
  5. 5 Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, United States;
  6. 6 Jerome Lipper Multiple Myeloma Center, Dana-Farber Cancer Institute, Boston, MA, United States;
  7. 7 Department of Pathology, Brigham and Women's Hospital, Boston, MA, United States
  1. * Corresponding author; email: steven_treon{at}
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.