title: Detection of MYD88 L265P in peripheral blood of patients with Waldenström's Macroglobulinemia and IgM monoclonal gammopathy of undetermined significance.
abstract: MYD88 L265P is highly prevalent in Waldenstrom's Macroglobulinemia (WM) and IgM monoclonal gammopathy of unknown significance (MGUS). We investigated whether MYD88 L265P could be identified by peripheral blood (PB) allele-specific PCR. MYD88 L265P was detected in untreated WM (114/118; 96.6%); previously treated WM (63/102; 61.8%); and IgM MGUS (5/12; 41.7%) but in none of 3 hyper-IgM or 40 healthy individuals. Median PB MYD88 L265P ΔCt was 3.77, 7.24, 10.89, 12.33 and 14.07 for untreated WM, previously treated WM, IgM MGUS, hyper-IgM and healthy individuals, respectively (P<0.0001). For the 232 IgM MGUS and WM patients, PB MYD88 L265P ΔCt moderately correlated to bone marrow (BM) disease (r=-0.3553; P<0.0001), serum IgM (r=-0.3262; P<0.0001) and hemoglobin (r=0.3005; P<0.0001) levels. PB MYD88 L265P ΔCt and serum IgM correlated similarly with BM disease burden. For positive patients, PB MYD88 L265P ΔCt was <6.5 in 100/114 (88%) untreated WM, and >6.5 in 4/5 (80%) IgM MGUS patients (P=0.0034). Attainment of a negative PB MYD88 L265P mutation status was associated with lower BM disease (P=0.001), serum IgM (P=0.019) and higher hemoglobin (P=0.004) levels in treated patients. These studies show the feasibility for detecting MYD88 L265P by PB examination, and the potential for PB MYD88 L265P ΔCt use in the diagnosis and management of WM patients.
authors: 1] Bing Center for Waldenström's Macroglobulinemia, Dana-Farber Cancer Institute, Boston, MA, USA [2] Department of Medicine, Harvard Medical School, Boston, MA, USA.
authors: L
authors: L
authors: Xu
authors: 1] Bing Center for Waldenström's Macroglobulinemia, Dana-Farber Cancer Institute, Boston, MA, USA [2] Department of Medicine, Harvard Medical School, Boston, MA, USA.
authors: Z R
authors: ZR
authors: Hunter
authors: 1] Bing Center for Waldenström's Macroglobulinemia, Dana-Farber Cancer Institute, Boston, MA, USA [2] Department of Medicine, Harvard Medical School, Boston, MA, USA.
authors: G
authors: G
authors: Yang
authors: 1] Bing Center for Waldenström's Macroglobulinemia, Dana-Farber Cancer Institute, Boston, MA, USA [2] Department of Medicine, Harvard Medical School, Boston, MA, USA.
authors: Y
authors: Y
authors: Cao
authors: 1] Bing Center for Waldenström's Macroglobulinemia, Dana-Farber Cancer Institute, Boston, MA, USA [2] Department of Medicine, Harvard Medical School, Boston, MA, USA.
authors: X
authors: X
authors: Liu
authors: Bing Center for Waldenström's Macroglobulinemia, Dana-Farber Cancer Institute, Boston, MA, USA.
authors: R
authors: R
authors: Manning
authors: Bing Center for Waldenström's Macroglobulinemia, Dana-Farber Cancer Institute, Boston, MA, USA.
authors: C
authors: C
authors: Tripsas
authors: Bing Center for Waldenström's Macroglobulinemia, Dana-Farber Cancer Institute, Boston, MA, USA.
authors: J
authors: J
authors: Chen
authors: Bing Center for Waldenström's Macroglobulinemia, Dana-Farber Cancer Institute, Boston, MA, USA.
authors: C J
authors: CJ
authors: Patterson
authors: 1] Department of Medicine, Harvard Medical School, Boston, MA, USA [2] Department of Pathology, Brigham and Women's Hospital, Boston, MA, USA.
authors: M
authors: M
authors: Kluk
authors: Bing Center for Waldenström's Macroglobulinemia, Dana-Farber Cancer Institute, Boston, MA, USA.
authors: S
authors: S
authors: Kanan
authors: 1] Bing Center for Waldenström's Macroglobulinemia, Dana-Farber Cancer Institute, Boston, MA, USA [2] Department of Medicine, Harvard Medical School, Boston, MA, USA.
authors: J
authors: J
authors: Castillo
authors: 1] Department of Medicine, Harvard Medical School, Boston, MA, USA [2] Department of Pathology, Brigham and Women's Hospital, Boston, MA, USA.
authors: N
authors: N
authors: Lindeman
authors: 1] Bing Center for Waldenström's Macroglobulinemia, Dana-Farber Cancer Institute, Boston, MA, USA [2] Department of Medicine, Harvard Medical School, Boston, MA, USA.
authors: S P
authors: SP
authors: Treon
mesh_terms: D018941:Antigens, CD19 / Q000032:analysis; D006454:Hemoglobins / Q000032:analysis; D006801:Humans; D007075:Immunoglobulin M / Q000097:blood*; D008998:Monoclonal Gammopathy of Undetermined Significance / Q000097:blood / Q000235:genetics*; D009154:Mutation; D053594:Myeloid Differentiation Factor 88 / Q000097:blood / Q000235:genetics*; D008258:Waldenstrom Macroglobulinemia / Q000097:blood / Q000235:genetics*
chemical_list: D018941:Antigens, CD19; D006454:Hemoglobins; D007075:Immunoglobulin M; C507779:MYD88 protein, human; D053594:Myeloid Differentiation Factor 88