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Leukemia. 2014 Jan;28(1):166-73. doi: 10.1038/leu.2013.124. Epub 2013 Apr 22.

Multiparameter flow cytometry for the identification of the Waldenström's clone in IgM-MGUS and Waldenström's Macroglobulinemia: new criteria for differential diagnosis and risk stratification.

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  • 11] Hospital Universitario de Salamanca, Department of Hematology, Salamanca, Spain [2] IBSAL IBMCC (USAL-CSIC), Salamanca, Spain.
  • 2Hospital Universitario de Salamanca, Department of Hematology, Salamanca, Spain.
  • 3Complejo Hospitalario de León, León, Spain.
  • 4Hospital Clínico Universitario de Valladolid, Valladolid, Spain.
  • 5Hospital Comarcal del Bierzo, PonferradaLeón, Spain.
  • 6Hospital General de Segovia, Segovia, Spain.
  • 7Hospital Virgen de la Concha, Zamora, Spain.
  • 8Hospital Virgen del Puerto, Plasencia, Spain.
  • 9Hospital Nuestra Señora de Sonsoles, Ávila, Spain.
  • 10Hospital Rio Carrión, Palencia, Spain.
  • 11Hospital Santos Reyes, Aranda de Duero, Spain.
  • 12Complejo Asistencial Universitario de Burgos, Burgos, Spain.
  • 131] IBSAL IBMCC (USAL-CSIC), Salamanca, Spain [2] Servicio General de Citometría and Departamento de Medicina, Universidad de Salamanca, Salamanca, Spain.


Although multiparameter flow cytometry (MFC) has demonstrated clinical relevance in monoclonal gammopathy of undetermined significance (MGUS)/myeloma, immunophenotypic studies on the full spectrum of Waldenström's Macroglobulinemia (WM) remain scanty. Herein, a comprehensive MFC analysis on bone marrow samples from 244 newly diagnosed patients with an immunoglobulin M (IgM) monoclonal protein was performed, including 67 IgM-MGUS, 77 smoldering and 100 symptomatic WM. Our results show a progressive increase on the number and light-chain-isotype-positive B-cells from IgM-MGUS to smoldering and symptomatic WM (P<.001), with only 1% of IgM-MGUS patients showing >10% B cells or 100% light-chain-isotype-positive B-cells (P<.001). Complete light-chain restriction of the B-cell compartment was an independent prognostic factor for time-to progression in smoldering WM (median 26 months; HR: 19.8, P=0.001) and overall survival in symptomatic WM (median 44 months; HR: 2.6, P=0.004). The progressive accumulation of light-chain-isotype-positive B-cells accompanied the emergence of a characteristic Waldenstrom's phenotype (CD22(+dim) / CD25+ /CD27+ / IgM+) that differed from other B-NHL by negative expression of CD5, CD10, CD11c or CD103. In contrast to myeloma, light-chain-isotype-positive plasma cells in IgM monoclonal gammopathies show otherwise normal antigenic expression. Our results highlight the potential value of MFC immunophenotyping for the characterization of the Waldenström's clone, as well as for the differential diagnosis, risk of progression and survival in WM.

[PubMed - indexed for MEDLINE]
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