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Lymphoma

IGHV gene features and MYD88 L265P mutation separate the three marginal zone lymphoma entities and Waldenström macroglobulinemia/lymphoplasmacytic lymphomas

Leukemia volume 27, pages 183–189 (2013)Cite this article

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Abstract

To clarify the relationships between marginal zone lymphomas (MZLs) and Waldenström macroglobulinemia/lymphoplasmacytic lymphomas (WM/LPLs), immunoglobulin heavy chain variable gene (IGHV) features were analyzed and the occurrence of MYD88 L265P mutations was identified in a series of 123 patients: 53 MZLs from the spleen (SMZLs), 11 from lymph nodes (NMZLs), 28 mucosa-associated lymphatic tissue (MALT) lymphomas and 31 WM/LPLs. SMZLs were characterized by overrepresentation of IGHV1–2 gene rearrangements with a canonical motif, without selection pressure and with long CDR3 segments. NMZLs had increased frequencies of IGHV3 genes. The IGHV gene was unmutated in most cases, often with long CDR3 segments. MALT lymphomas were usually associated with a mutated IGHV gene, but with the absence of selection pressure. WM/LPLs were associated with an IGHV3–23 overrepresentation and high IGHV mutation rate, with features of selection pressure and short CDR3 segments. MYD88 L265P mutations were almost restricted exclusively to WM/LPL patients. Taken all diagnoses together, all patients with MYD88 L265P mutations had an immunoglobulin M peak and almost all patients except one had bone marrow infiltration. These results demonstrate that the history of antigen exposure of the four entities studied was different and MYD88 L265P was specifically associated with WM/LPLs. WM/LPL may thus be functionally associated with constitutive nuclear factor-κB activation.

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Acknowledgements

We thank Dr Jeanne Cook-Moreau for careful re-reading of the manuscript and English editing. We thank the French tumor banks of hospital university campus of Limoges, Bordeaux and Montpellier as well as Institut Bergonié (France) for providing biological material. We are grateful to Pr Frédéric Davi (Laboratoire d’Hématologie, CHU Pitié-Salpétrière, Paris, France) for helpful scientific discussions. This work was supported by Comités Limousin Ligue contre le Cancer, Comité Orientation de la Recherche en Cancérologie (CORC Limousin) and Institut National du Cancer (ACI Program 2007 and PAIR program 2008). We thank Dr Florence Bosselut (Laboratoire d’Hématologie, CHU Dupuytren, Limoges, France) for monitoring clinical data. Finally, we thank the reviewers for their very helpful suggestions.

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Authors and Affiliations

  1. Laboratoires d’Hématologie et d’Immunologie, CHU de Limoges, Limoges and Centre National de la Recherche Scientifique, UMR CNRS 7276, Faculté de Médecine de Limoges, Université de Limoges, Limoges, France

    N Gachard, A Marfak, D Rizzo, M Devesa, M P Laforêt, M Cogné & J Feuillard

  2. Département de Pathologie et de Biologie Moléculaire, EA 2406 CHU and University of Bordeaux 2,

    M Parrens & A de Mascarel

  3. Bordeaux, France

    M Parrens & A de Mascarel

  4. Département de Pathologie, Institut Bergonié, Bordeaux, France

    I Soubeyran

  5. Laboratoire d’Anatomie Pathologique, CHU Limoges, Limoges, France

    B Petit & M Delage-Corre

  6. Laboratoire d’Anatomie Pathologique, Hôpital Gui de Chauliac, Montpellier, France

    V Coste

  7. Service de biologie des tumeurs–Tumorothèque, CHU Bordeaux–Haut Levêque, Bordeaux, France

    J P Merlio

  8. Service d’hématologie clinique et de thérapies ciblées, CHU de Bordeaux et Université de Bordeaux 2, Hopital Haut Lévêque, Pessac, France

    K Bouabdhalla & N Milpied

  9. Département d’Oncologie médicale, Institut Bergonié, Bordeaux, France

    P Soubeyran & A Schmitt

  10. Service d’Hématologie Clinique, CHU de Limoges, Limoges, France

    D Bordessoule

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Correspondence to J Feuillard.

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Gachard, N., Parrens, M., Soubeyran, I. et al. IGHV gene features and MYD88 L265P mutation separate the three marginal zone lymphoma entities and Waldenström macroglobulinemia/lymphoplasmacytic lymphomas. Leukemia 27, 183–189 (2013). https://doi.org/10.1038/leu.2012.257

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