title: MYD88 L265P is a marker highly characteristic of, but not restricted to, Waldenström's macroglobulinemia.
abstract: We evaluated the MYD88 L265P mutation in Waldenström's macroglobulinemia (WM) and B-cell lymphoproliferative disorders by specific polymerase chain reaction (PCR) (sensitivity ∼10(-3)). No mutation was seen in normal donors, while it was present in 101/117 (86%) WM patients, 27/31 (87%) IgM monoclonal gammapathies of uncertain significance (MGUS), 3/14 (21%) splenic marginal zone lymphomas and 9/48 (19%) non-germinal center (GC) diffuse large B-cell lymphomas (DLBCLs). The mutation was absent in all 28 GC-DLBCLs, 13 DLBCLs not subclassified, 35 hairy cell leukemias, 39 chronic lymphocytic leukemias (16 with M-component), 25 IgA or IgG-MGUS, 24 multiple myeloma (3 with an IgM isotype), 6 amyloidosis, 9 lymphoplasmacytic lymphomas and 1 IgM-related neuropathy. Among WM and IgM-MGUS, MYD88 L265P mutation was associated with some differences in clinical and biological characteristics, although usually minor; wild-type MYD88 cases had smaller M-component (1.77 vs 2.72 g/dl, P=0.022), more lymphocytosis (24 vs 5%, P=0.006), higher lactate dehydrogenase level (371 vs 265 UI/L, P=0.002), atypical immunophenotype (CD23-CD27+ +FMC7+ +), less Immunoglobulin Heavy Chain Variable gene (IGHV) somatic hypermutation (57 vs 97%, P=0.012) and less IGHV3-23 gene selection (9 vs 27%, P=0.014). These small differences did not lead to different time to first therapy, response to treatment or progression-free or overall survival.
authors: Department of Hematology, University Hospital of Salamanca, Salamanca, Spain.
authors: C
authors: C
authors: Jiménez
authors: E
authors: E
authors: Sebastián
authors: M C
authors: MC
authors: Chillón
authors: P
authors: P
authors: Giraldo
authors: J
authors: J
authors: Mariano Hernández
authors: F
authors: F
authors: Escalante
authors: T J
authors: TJ
authors: González-López
authors: C
authors: C
authors: Aguilera
authors: A G
authors: AG
authors: de Coca
authors: I
authors: I
authors: Murillo
authors: M
authors: M
authors: Alcoceba
authors: A
authors: A
authors: Balanzategui
authors: M E
authors: ME
authors: Sarasquete
authors: R
authors: R
authors: Corral
authors: L A
authors: LA
authors: Marín
authors: B
authors: B
authors: Paiva
authors: E M
authors: EM
authors: Ocio
authors: N C
authors: NC
authors: Gutiérrez
authors: M
authors: M
authors: González
authors: J F
authors: JF
authors: San Miguel
authors: R
authors: R
authors: García-Sanz
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D015415:Biomarkers / Q000378:metabolism; D018450:Disease Progression; D006801:Humans; D007075:Immunoglobulin M / Q000378:metabolism; D008232:Lymphoproliferative Disorders / Q000175:diagnosis / Q000235:genetics / Q000378:metabolism; D008875:Middle Aged; D009154:Mutation; D053594:Myeloid Differentiation Factor 88 / Q000235:genetics* / Q000378:metabolism; D018365:Neoplasm, Residual / Q000175:diagnosis / Q000235:genetics; D008258:Waldenstrom Macroglobulinemia / Q000175:diagnosis / Q000235:genetics* / Q000378:metabolism / Q000401:mortality
chemical_list: D015415:Biomarkers; D007075:Immunoglobulin M; D053594:Myeloid Differentiation Factor 88