title: MYD88 L265P and CXCR4 mutations in lymphoplasmacytic lymphoma identify cases with high disease activity.
abstract: Recurrent mutations in MYD88 have been identified in >90% of lymphoplasmacytic lymphoma (LPL). Recently, WHIM (warts, hypogammaglobulinaemia, infections, myelokathexis) syndrome-like mutations in CXCR4 have been described in 28% of LPL cases, and seem to impact clinical presentation and response to therapy. We investigated the presence of the MYD88 L265P mutation in 90 decalcified, formalin-fixed, paraffin-embedded (FFPE) bone marrow (BM) biopsies, including 51 cases of LPL, 14 cases of B-cell chronic lymphocytic leukaemia (CLL), 13 cases of marginal zone lymphoma (MZL) and 12 normal controls. In addition, the C-terminal domain of CXCR4 was sequenced in LPL cases. MYD88 L265P was found in 49/51 (96%) LPL cases and in 1/13 (7·6%) MZL (splenic type), whereas all CLL samples remained negative. The two MYD88 wild type LPL cases were associated with cold agglutinin disease. Mutations in CXCR4 were detected in 17/47 (36·2%) LPL cases, which showed a higher extent of BM infiltration and lower leucocyte counts (P = 0·02), haemoglobin (P = 0·05) and platelet counts (P = 0·01). In conclusion the detection of MYD88 L265P mutation in FFPE samples is reliable and useful for subtyping small B-cell lymphomas in BM biopsies. In addition, the presence of CXCR4 mutations identifies a subgroup of LPL patients with higher disease activity.
authors.affiliation: Institute of Pathology and Comprehensive Cancer Centre, Eberhard-Karls-University, University Hospital Tübingen, Tübingen, Germany.
authors.forename: Janine
authors.initials: J
authors.lastname: Schmidt
authors.affiliation: Institute of Pathology and Comprehensive Cancer Centre, Eberhard-Karls-University, University Hospital Tübingen, Tübingen, Germany.
authors.forename: Birgit
authors.initials: B
authors.lastname: Federmann
authors.affiliation: Institute of Pathology and Comprehensive Cancer Centre, Eberhard-Karls-University, University Hospital Tübingen, Tübingen, Germany.
authors.forename: Natalie
authors.initials: N
authors.lastname: Schindler
authors.affiliation: Institute of Pathology and Comprehensive Cancer Centre, Eberhard-Karls-University, University Hospital Tübingen, Tübingen, Germany.
authors.forename: Julia
authors.initials: J
authors.lastname: Steinhilber
authors.affiliation: Institute of Pathology and Comprehensive Cancer Centre, Eberhard-Karls-University, University Hospital Tübingen, Tübingen, Germany.
authors.forename: Irina
authors.initials: I
authors.lastname: Bonzheim
authors.affiliation: Institute of Pathology and Comprehensive Cancer Centre, Eberhard-Karls-University, University Hospital Tübingen, Tübingen, Germany.
authors.forename: Falko
authors.initials: F
authors.lastname: Fend
authors.affiliation: Institute of Pathology and Comprehensive Cancer Centre, Eberhard-Karls-University, University Hospital Tübingen, Tübingen, Germany.
authors.forename: Leticia
authors.initials: L
authors.lastname: Quintanilla-Martinez
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D019943:Amino Acid Substitution; D001853:Bone Marrow / Q000473:pathology; D005260:Female; D006801:Humans; D016393:Lymphoma, B-Cell / Q000235:genetics; D008297:Male; D008875:Middle Aged; D009154:Mutation; D053594:Myeloid Differentiation Factor 88 / Q000235:genetics*; D016133:Polymerase Chain Reaction; D011379:Prognosis; D019718:Receptors, CXCR4 / Q000235:genetics*; D012680:Sensitivity and Specificity; D008258:Waldenstrom Macroglobulinemia / Q000175:diagnosis* / Q000235:genetics*
chemical_list: D053594:Myeloid Differentiation Factor 88; D019718:Receptors, CXCR4
keywords: CXCR4; MYD88 L265P; WHIM; cold agglutinin disease; lymphoplasmacytic lymphoma