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Clone-specific MYD88 L265P and CXCR4 mutation status can provide clinical utility in suspected Waldenström macroglobulinemia/lymphoplasmacytic lymphoma.
Leuk Res. 2016 12; 51:41-48.LR

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+Show Affiliations

Hematologics Inc, 3161 Elliott Avenue, Suite 200, Seattle, WA, 98121, USA.Hematologics Inc, 3161 Elliott Avenue, Suite 200, Seattle, WA, 98121, USA.Hematologics Inc, 3161 Elliott Avenue, Suite 200, Seattle, WA, 98121, USA.Hematologics Inc, 3161 Elliott Avenue, Suite 200, Seattle, WA, 98121, USA.Hematologics Inc, 3161 Elliott Avenue, Suite 200, Seattle, WA, 98121, USA.Hematologics Inc, 3161 Elliott Avenue, Suite 200, Seattle, WA, 98121, USA.Hematologics Inc, 3161 Elliott Avenue, Suite 200, Seattle, WA, 98121, USA.Hematologics Inc, 3161 Elliott Avenue, Suite 200, Seattle, WA, 98121, USA.Hematologics Inc, 3161 Elliott Avenue, Suite 200, Seattle, WA, 98121, USA.Hematologics Inc, 3161 Elliott Avenue, Suite 200, Seattle, WA, 98121, USA. Electronic address: Barbara@hematologics.com.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

27890075

Citation

Burnworth, Bettina, et al. "Clone-specific MYD88 L265P and CXCR4 Mutation Status Can Provide Clinical Utility in Suspected Waldenström Macroglobulinemia/lymphoplasmacytic Lymphoma." Leukemia Research, vol. 51, 2016, pp. 41-48.
Burnworth B, Wang Z, Singleton TP, et al. Clone-specific MYD88 L265P and CXCR4 mutation status can provide clinical utility in suspected Waldenström macroglobulinemia/lymphoplasmacytic lymphoma. Leuk Res. 2016;51:41-48.
Burnworth, B., Wang, Z., Singleton, T. P., Bennington, A., Fritschle, W., Bennington, R., Brodersen, L. E., Wells, D. A., Loken, M. R., & Zehentner, B. K. (2016). Clone-specific MYD88 L265P and CXCR4 mutation status can provide clinical utility in suspected Waldenström macroglobulinemia/lymphoplasmacytic lymphoma. Leukemia Research, 51, 41-48. https://doi.org/10.1016/j.leukres.2016.10.008
Burnworth B, et al. Clone-specific MYD88 L265P and CXCR4 Mutation Status Can Provide Clinical Utility in Suspected Waldenström Macroglobulinemia/lymphoplasmacytic Lymphoma. Leuk Res. 2016;51:41-48. PubMed PMID: 27890075.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Clone-specific MYD88 L265P and CXCR4 mutation status can provide clinical utility in suspected Waldenström macroglobulinemia/lymphoplasmacytic lymphoma. AU - Burnworth,Bettina, AU - Wang,Zhixing, AU - Singleton,Timothy P, AU - Bennington,Angela, AU - Fritschle,Wayne, AU - Bennington,Richard, AU - Brodersen,Lisa Eidenschink, AU - Wells,Denise A, AU - Loken,Michael R, AU - Zehentner,Barbara K, Y1 - 2016/10/18/ PY - 2016/08/18/received PY - 2016/10/10/revised PY - 2016/10/17/accepted PY - 2016/11/29/entrez PY - 2016/11/29/pubmed PY - 2017/6/14/medline KW - CXCR4 KW - Flow cytometric cell sorting KW - Lymphoplasmacytic lymphoma KW - MYD88L256P KW - Waldenström’s macroglobulinemia SP - 41 EP - 48 JF - Leukemia research JO - Leuk. Res. VL - 51 N2 - 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. SN - 1873-5835 UR - https://www.unboundmedicine.com/medline/citation/27890075/Clone_specific_MYD88_L265P_and_CXCR4_mutation_status_can_provide_clinical_utility_in_suspected_Waldenström_macroglobulinemia/lymphoplasmacytic_lymphoma_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0145-2126(16)30219-3 DB - PRIME DP - Unbound Medicine ER -