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Myeloma

MYD88 L265P is a marker highly characteristic of, but not restricted to, Waldenström’s macroglobulinemia

Leukemia volume 27, pages 1722–1728 (2013)Cite this article

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Abstract

We evaluated the MYD88 L265P mutation in Waldenström’s macroglobulinemia (WM) and B-cell lymphoproliferative disorders by specific polymerase chain reaction (PCR) (sensitivity ∼10−3). No mutation was seen in normal donors, while it was present in 101/117 (86%) WM patients, 27/31 (87%) IgM monoclonal gammapathies of uncertain significance (MGUS), 3/14 (21%) splenic marginal zone lymphomas and 9/48 (19%) non-germinal center (GC) diffuse large B-cell lymphomas (DLBCLs). The mutation was absent in all 28 GC-DLBCLs, 13 DLBCLs not subclassified, 35 hairy cell leukemias, 39 chronic lymphocytic leukemias (16 with M-component), 25 IgA or IgG-MGUS, 24 multiple myeloma (3 with an IgM isotype), 6 amyloidosis, 9 lymphoplasmacytic lymphomas and 1 IgM-related neuropathy. Among WM and IgM-MGUS, MYD88 L265P mutation was associated with some differences in clinical and biological characteristics, although usually minor; wild-type MYD88 cases had smaller M-component (1.77 vs 2.72 g/dl, P=0.022), more lymphocytosis (24 vs 5%, P=0.006), higher lactate dehydrogenase level (371 vs 265 UI/L, P=0.002), atypical immunophenotype (CD23−CD27++FMC7++), less Immunoglobulin Heavy Chain Variable gene (IGHV) somatic hypermutation (57 vs 97%, P=0.012) and less IGHV3–23 gene selection (9 vs 27%, P=0.014). These small differences did not lead to different time to first therapy, response to treatment or progression-free or overall survival.

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Acknowledgements

We thank Alicia Antón and Rebeca Maldonado for their technical assistance and Phill Mason for checking the English usage and grammar of the manuscript. This work has been partially supported by the grant number PS09/01450 from the Spanish ‘Fondo de Investigaciones Sanitarias’ and the grant reference HUS412A12-1 from the ‘Consejería de Educación de la Junta de Castilla y León’.

Authors contributions

Cristina Jiménez and Ramón García-Sanz were the initial designers of the study. Cristina Jiménez, Elena Sebastián, María del Carmen Chillón and Ana Balanzategui carried out all molecular studies and prepared the database for the final analysis. Ramón García-Sanz desgined the database, and Miguel Alcoceba helped to handle it and to develop the initial analysis. Ramón García-Sanz helped by Luis A Marín developed the statistical analysis. Pilar Giraldo, José Mariano Hernández, Fernando Escalante, Tomás J González-López, Carmen Aguilera, Alfonso García de Coca, Ilda Murillo and Marcos González were clinicians responsible for the patients and those who took care of the protocols’ accomplishment, sampling and collection of clinical data. Rocío Corral and María Eugenia Sarasquete helped in the molecular analysis and data collection. Bruno Paiva, Enrique M Ocio and Norma C Gutiérrez were responsible for the immunophenotyping and ctyogenetic analysis of the patients included in this series. Ramón García-Sanz and Cristina Jiménez prepared the initial version of the paper. Jesús F San Miguel and Marcos González were the main responsible of the global and molecular groups, respectively, and they were the persons responsible of the final revision of the draft, as well as the ones who gave the final approval of the version to be published. Ramón García-Sanz reviewed the conception and design of most of the work, made the database and supervised the statistical analysis. He rewrote the paper and made the final upload of the paper.

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Authors and Affiliations

  1. Department of Hematology, University Hospital of Salamanca, Salamanca, Spain

    C Jiménez, E Sebastián, M C Chillón, M Alcoceba, A Balanzategui, M E Sarasquete, R Corral, L A Marín, B Paiva, E M Ocio, N C Gutiérrez, M González, J F San Miguel & R García-Sanz

  2. Center of Investigation in Cancer (CIC), Instituto Biosanitario de Salamanca (IBSAL), Salamanca, Spain

    M C Chillón, M E Sarasquete, B Paiva, E M Ocio, N C Gutiérrez, M González, J F San Miguel & R García-Sanz

  3. Department of Hematology, Hospital Miguel Servet, Zaragoza, Spain

    P Giraldo & I Murillo

  4. Department of Hematology, Hospital General, Segovia, Spain

    J Mariano Hernández

  5. Department of Hematology, Hospital Virgen Blanca, León, Spain

    F Escalante

  6. Department of Hematology, Hospital General de Burgos, Burgos, Spain

    T J González-López

  7. Department of Hematology, Hospital Comarcal del Bierzo, León, Spain

    C Aguilera

  8. Department of Hematology, Hospital Clínico, Valladolid, Spain

    A G de Coca

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  1. C Jiménez
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Correspondence to R García-Sanz.

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Jiménez, C., Sebastián, E., Chillón, M. et al. MYD88 L265P is a marker highly characteristic of, but not restricted to, Waldenström’s macroglobulinemia. Leukemia 27, 1722–1728 (2013). https://doi.org/10.1038/leu.2013.62

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