Open AccessDetection of MYD88 L265P mutation by next-generation deep sequencing in peripheral blood mononuclear cells of Waldenström’s macroglobulinemia and IgM monoclonal gammopathy of undetermined significance
Author(s) -
Ayako Nakamura,
Chikako Ohwada,
Masahiro Takeuchi,
Yusuke Takeda,
Shokichi Tsukamoto,
Naoya Mimura,
Nagisa Oshima-Hasegawa,
Yoshiaki Sugita,
Hiroaki Tanaka,
Hisashi Wakita,
Nobuyuki Aotsuka,
Kosei Matsue,
Koutaro Yokote,
Osamu Ohara,
Chiaki Nakaseko,
Emiko Sakaida
Publication year - 2019
Publication title -
plos one
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.99
H-Index - 332
ISSN - 1932-6203
DOI - 10.1371/journal.pone.0221941
Subject(s) - peripheral blood mononuclear cell , waldenstrom macroglobulinemia , macroglobulinemia , medicine , monoclonal gammopathy of undetermined significance , immunoglobulin m , gammopathy , immunology , monoclonal , pathology , gastroenterology , multiple myeloma , biology , antibody , monoclonal antibody , immunoglobulin g , genetics , lymphoma , in vitro
We investigated the feasibility of using next-generation sequencing (NGS) technique using molecular barcoding technology to detect MYD88 L265P mutation in unselected peripheral blood mononuclear cells (PBMCs) in 52 patients with Waldenström’s macroglobulinemia [1] and 21 patients with IgM-monoclonal gammopathy of undetermined significance (MGUS). The NGS technique successfully detected the MYD88 L265P in unselected PBMCs at a sensitivity of 0.02%, which was ×5 higher than that of AS-PCR. All the results between paired BM and PB samples from 2 IgM MGUS and 4 untreated WM patients matched completely. MYD88 L265P mutation was detected in 14/21 (66.7%), 14/19 (73.7%), and 10/33 (30.3%) with the median mutant allele burden of 0.36% (range, 0.06–2.85%), 0.48% (range, 0.02–32.3%), and 0.16% (range, 0.02–33.8%), in IgM-MGUS, untreated WM, and previously treated WM, respectively. Multiple linear regression analysis identified an absolute peripheral lymphocyte count as the positive predictor of PB mutant allele burden (R2 = 0,72, P<0.0001). Our non-invasive, simple NGS method has the potential to detect MYD88 L265P mutations in PBMCs of IgM MGUS and WM patients, which may especially utilized for monitoring minimal residual tumor burden after treatment.