1. MYD88 L265P in Waldenström macroglobulinemia, immunoglobulin M monoclonal gaminopathy, and other B-cell lymphoproliferative disorders using conventional and quantitative allele-specific polymerase chain reaction.
- Author
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Lian Xu, Hunter, Zachary R., Guang Yang, Yangsheng Zhou, Yang Cao, Xia Liu, Morra, Enrica, Trojani, Alessandra, Greco, Antonino, Arcaini, Luca, Varettoni, Maria, Brown, Jennifer R., Yu-Tzu Tai, Anderson, Kenneth C., Munshi, Nikhil C., Patterson, Christopher J., Manning, Robert J., Tripsas, Christina K., Lindeman, Neal I., and Treon, Steven P.
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IMMUNOGLOBULIN M , *LYMPHOPROLIFERATIVE disorders , *B cells , *POLYMERASE chain reaction , *ALLELES - 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 macroglobutinemia (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 C MGUS (0/9) patientsas 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. [ABSTRACT FROM AUTHOR]
- Published
- 2013
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