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Clone-specific MYD88 L265P and CXCR4 mutation status can provide clinical utility in suspected Waldenström macroglobulinemia/lymphoplasmacytic lymphoma.
Burnworth, Bettina; Wang, Zhixing; Singleton, Timothy P; Bennington, Angela; Fritschle, Wayne; Bennington, Richard; Brodersen, Lisa Eidenschink; Wells, Denise A; Loken, Michael R; Zehentner, Barbara K.
Afiliación
  • Burnworth B; Hematologics Inc, 3161 Elliott Avenue, Suite 200, Seattle, WA, 98121, USA.
  • Wang Z; Hematologics Inc, 3161 Elliott Avenue, Suite 200, Seattle, WA, 98121, USA.
  • Singleton TP; Hematologics Inc, 3161 Elliott Avenue, Suite 200, Seattle, WA, 98121, USA.
  • Bennington A; Hematologics Inc, 3161 Elliott Avenue, Suite 200, Seattle, WA, 98121, USA.
  • Fritschle W; Hematologics Inc, 3161 Elliott Avenue, Suite 200, Seattle, WA, 98121, USA.
  • Bennington R; Hematologics Inc, 3161 Elliott Avenue, Suite 200, Seattle, WA, 98121, USA.
  • Brodersen LE; Hematologics Inc, 3161 Elliott Avenue, Suite 200, Seattle, WA, 98121, USA.
  • Wells DA; Hematologics Inc, 3161 Elliott Avenue, Suite 200, Seattle, WA, 98121, USA.
  • Loken MR; Hematologics Inc, 3161 Elliott Avenue, Suite 200, Seattle, WA, 98121, USA.
  • Zehentner BK; Hematologics Inc, 3161 Elliott Avenue, Suite 200, Seattle, WA, 98121, USA. Electronic address: Barbara@hematologics.com.
Leuk Res ; 51: 41-48, 2016 12.
Article en En | MEDLINE | ID: mdl-27890075
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.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Biomarcadores de Tumor / Macroglobulinemia de Waldenström / Receptores CXCR4 / Factor 88 de Diferenciación Mieloide Tipo de estudio: Diagnostic_studies Límite: Aged / Aged80 / Female / Humans / Male / Middle aged Idioma: En Revista: Leuk Res Año: 2016 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Reino Unido
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Biomarcadores de Tumor / Macroglobulinemia de Waldenström / Receptores CXCR4 / Factor 88 de Diferenciación Mieloide Tipo de estudio: Diagnostic_studies Límite: Aged / Aged80 / Female / Humans / Male / Middle aged Idioma: En Revista: Leuk Res Año: 2016 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Reino Unido