title: Clone-specific MYD88 L265P and CXCR4 mutation status can provide clinical utility in suspected Waldenström macroglobulinemia/lymphoplasmacytic lymphoma.
abstract: MYD88 L265P, a diagnostic marker for lymphoplasmacytic lymphoma (LPL)/Waldenström macroglobulinemia (WM) can also be detected in other hematopoietic malignancies. We demonstrate a novel approach to increase the specificity of this marker for WM/LPL diagnosis by combining flow cytometric cell sorting with molecular analysis. Clonal B-lymphocyte and co-occurring clonal plasma cell populations of low-grade B-cell lymphomas were sorted by flow cytometry and analyzed for immunoglobulin gene rearrangements (PCR), and for MYD88 and CXCR4 mutations. Identical clonal origin was confirmed by PCR for 21 LPL/WM cases and MYD88 L265P was detected in both B-cell and plasma cell fractions. 9/20 other B-cell lymphomas with identical light chain restriction on B-cells and plasma cells were genotypically identical by PCR and MYD88 L265P was detected in both cell fractions in 7/9 whereas in 11/20 specimens with different clonal origin, MYD88 L265P was absent (5/11), or only found in B-lymphocytes (4/11), or plasma cells (2/11). CXCR4 mutations were detected in 17/39 cases, but missed in 63% of these without cell sorting. Confirming MYD88L265P in both B-cells and plasma cell fractions can provide a novel and powerful discriminator to distinguish LPL/WM from phenotypically similar disorders. Furthermore, this approach significantly increases CXCR4 detection sensitivity.
authors.affiliation: Hematologics Inc, 3161 Elliott Avenue, Suite 200, Seattle, WA, 98121, USA.
authors.forename: Bettina
authors.initials: B
authors.lastname: Burnworth
authors.affiliation: Hematologics Inc, 3161 Elliott Avenue, Suite 200, Seattle, WA, 98121, USA.
authors.forename: Zhixing
authors.initials: Z
authors.lastname: Wang
authors.affiliation: Hematologics Inc, 3161 Elliott Avenue, Suite 200, Seattle, WA, 98121, USA.
authors.forename: Timothy P
authors.initials: TP
authors.lastname: Singleton
authors.affiliation: Hematologics Inc, 3161 Elliott Avenue, Suite 200, Seattle, WA, 98121, USA.
authors.forename: Angela
authors.initials: A
authors.lastname: Bennington
authors.affiliation: Hematologics Inc, 3161 Elliott Avenue, Suite 200, Seattle, WA, 98121, USA.
authors.forename: Wayne
authors.initials: W
authors.lastname: Fritschle
authors.affiliation: Hematologics Inc, 3161 Elliott Avenue, Suite 200, Seattle, WA, 98121, USA.
authors.forename: Richard
authors.initials: R
authors.lastname: Bennington
authors.affiliation: Hematologics Inc, 3161 Elliott Avenue, Suite 200, Seattle, WA, 98121, USA.
authors.forename: Lisa Eidenschink
authors.initials: LE
authors.lastname: Brodersen
authors.affiliation: Hematologics Inc, 3161 Elliott Avenue, Suite 200, Seattle, WA, 98121, USA.
authors.forename: Denise A
authors.initials: DA
authors.lastname: Wells
authors.affiliation: Hematologics Inc, 3161 Elliott Avenue, Suite 200, Seattle, WA, 98121, USA.
authors.forename: Michael R
authors.initials: MR
authors.lastname: Loken
authors.affiliation: Hematologics Inc, 3161 Elliott Avenue, Suite 200, Seattle, WA, 98121, USA. Electronic address: Barbara@hematologics.com.
authors.forename: Barbara K
authors.initials: BK
authors.lastname: Zehentner
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D001402:B-Lymphocytes / Q000737:chemistry / Q000473:pathology; D014408:Biomarkers, Tumor / Q000032:analysis*; D002999:Clone Cells; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D053594:Myeloid Differentiation Factor 88 / Q000032:analysis* / Q000235:genetics; D010950:Plasma Cells / Q000737:chemistry / Q000473:pathology; D016133:Polymerase Chain Reaction; D019718:Receptors, CXCR4 / Q000032:analysis* / Q000235:genetics; D012680:Sensitivity and Specificity; D014407:Tumor Cells, Cultured; D008258:Waldenstrom Macroglobulinemia / Q000175:diagnosis* / Q000473:pathology
chemical_list: D014408:Biomarkers, Tumor; C527276:CXCR4 protein, human; C507779:MYD88 protein, human; D053594:Myeloid Differentiation Factor 88; D019718:Receptors, CXCR4
keywords: CXCR4; Flow cytometric cell sorting; Lymphoplasmacytic lymphoma; MYD88L256P; Waldenström’s macroglobulinemia