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MYD88 (L265P) mutation is an independent prognostic factor for outcome in patients with diffuse large B-cell lymphoma

Leukemia volume 28, pages 2104–2106 (2014)Cite this article

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Diffuse large B-cell lymphoma (DLBCL) encompasses an aggressive and heterogeneous group of malignancies. Gene expression profiling (GEP) unraveled two main subtypes based on their putative cell of origin named germinal center B-cell-like (GCB) and activated B-cell-like (ABC), with specific genetic alterations and different clinical outcome.1 Recent studies have reported several somatic mutations in the myeloid differentiation primary response gene 88 (MYD88) affecting B-cell lymphomas. Among them, the leucine to proline exchange at position 265 (L265P) is the most recurrent and biologically potent MYD88 variation, being found in about 30% of ABC-DLBCL but uncommon in GCB-DLBCL.2 Here, we have investigated the occurrence of MYD88 L265P mutation in adult patients with DLBCL and its relation to clinical and biological characteristics, including patients’ outcome.

A series of 175 retrospective patients diagnosed of DLBCL from July 2000 to July 2013 was selected from our lymphoma registry. To be included in this study, cases were required to have: newly diagnosed DLBCL that had not been previously treated with full clinical data available, treatment with remission intention, enough material for DNA extraction and absence of HIV infection. This study was approved by the local ethical committee and was conducted in accordance with the Declaration of Helsinki. Immunohistochemical staining was performed on formalin-fixed paraffin-embedded sections with the following antibodies: CD20 (clone L26, Dako, Glostrup, Denmark), CD10 (clone 56C6, Novocastra, Newcastle, UK), MUM1 (clone MUM1p, Dako), BCL2 (clone 100, BioGenex, San Ramon, CA, USA) and BCL6 (clone PG-B6p, Dako). MYD88 L265P mutation was assessed by allele-specific oligonucleotide PCR that can detect low levels of mutant DNA as previously described.3 Association with clinical characteristics was investigated by Fisher’s exact test for categorical data and t-test or Mann–Whitney U-test for continuous data. Overall survival (OS) and progression-free survival (PFS) were calculated since the time from first treatment and according to standard definitions. Kaplan–Meier survival estimates were obtained and multivariate Cox regression was used to determine whether mutation remained independently predictive of PFS and OS after adjusting for clinical variables. Significance was set at P⩽0.05.

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Acknowledgements

This work was supported by RD09/0076/0036, PT13/0010/0005, 2014 SGR 567 and the ‘Xarxa de Bancs de tumors’ sponsored by Pla Director d'Oncologia de Catalunya (XBTC). CF-R received a fellowship from the Ministry of Economy and Competitiveness of Spain (PFIS grant FI11/00353).

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Author notes

  1. C Fernández-Rodríguez and B Bellosillo: These authors contributed equally to this work.

Authors and Affiliations

  1. Grup de Recerca Clínica Aplicada en Neoplàsies Hematològiques-Hospital del Mar-IMIM, Barcelona, Spain

    C Fernández-Rodríguez, B Bellosillo, B Sánchez-González, E Gimeno, C Besses & A Salar

  2. Universitat Autònoma de Barcelona, Barcelona, Spain

    C Fernández-Rodríguez

  3. Department of Pathology, Hospital del Mar-IMIM, Barcelona, Spain

    B Bellosillo, M García-García, M C Vela & S Serrano

  4. Universitat Pompeu Fabra, Barcelona, Spain

    B Bellosillo

  5. Department of Hematology, Hospital del Mar-IMIM, Barcelona, Spain

    B Sánchez-González, E Gimeno, C Besses & A Salar

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  1. C Fernández-Rodríguez
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  2. B Bellosillo
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Correspondence to A Salar.

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Fernández-Rodríguez, C., Bellosillo, B., García-García, M. et al. MYD88 (L265P) mutation is an independent prognostic factor for outcome in patients with diffuse large B-cell lymphoma. Leukemia 28, 2104–2106 (2014). https://doi.org/10.1038/leu.2014.184

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