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Rapid detection of MYD88-L265P mutation by PCR-RFLP in B-cell lymphoproliferative disorders

Leukemia volume 28, pages 447–449 (2014)Cite this article

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Accumulating evidence suggests that chronic lymphocytic leukemia (CLL), multiple myeloma (MM) and Waldenstrom’s macroglobulinemia (WM) have been associated with precursor conditions, termed CD5+ monoclonal B-cell lymphocytosis (MBL) for CLL,1 and monoclonal gammopathy of undetermined significance (MGUS) for MM2 and WM.3 However, the outcome for MGUS seems to be different, depending on the class of immunoglobulin expression. Immunoglobulin type G (IgG) and immunoglobulin type A (IgA) MGUS progress to MM, while immunoglobulin type M (IgM) MGUS is considered to be a distinct biological and clinical entity, and has been reported to progress most often to WM.3 However, the point at which MGUS progresses to the above malignancies remains still vague.

Long-term follow-up of patients with IgM-MGUS reveals that they are at increased risk for WM,3 a B-cell lymphoproliferative disorder (BLD) characterized by lymphoplasmacytic cell infiltration in bone marrow (BM) and the presence of IgM monoclonal gammopathy in the serum.4 Although the pathogenesis of WM has not been defined, familial clustering suggests that genetic factors may have a role in the development of the disease.5 Recently, Treon et al.6 revealed a novel recurring mutation (L265P) in the myeloid differentiation primary response 88 (MYD88) gene in patients with WM. Whole-genome sequencing, confirmed by Sanger sequencing, revealed that approximately 90% of patients with WM and 100% with non–IgM-secreting lymphoplasmacytic lymphoma (LPL) carried the mutation.6 On the contrary, MYD88-L265P was absent in the paired normal tissue of the above patients, as well as in 10 patients with MM (including two with IgM-MM), but it was expressed in 7% of patients with marginal-zone lymphoma. Interestingly, it was found that only 2 of 21 patients with IgM-MGUS (10%) were positive for MYD88-L265P using Sanger sequencing, while one of them developed WM.6 Subsequently, the same group, using an allele-specific PCR (AS-PCR) protocol applied in BM samples, detected the mutation in 93% of patients with WM and in 54% of patients with IgM-MGUS,7 while Landgren et al.8 detected the MYD88-L265P mutation in CD19+ BM cells of 5 out of 9 IgM-MGUS patients (56%), by Sanger sequencing. Additional studies confirmed that MYD88-L265P is a marker highly characteristic of WM, but it is also rarely present in other BLD, as splenic lymphoma with villous lymphocytes (SLVL).9, 10

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Authors and Affiliations

  1. Department of Immunology and Histocompatibility, Faculty of Medicine, University of Thessaly, School of Health Sciences, Biopolis, Greece

    N Argentou, A E Germenis & M Speletas

  2. Department of Hematology, Faculty of Medicine, University of Thessaly, School of Health Sciences, Biopolis, Greece

    G Vassilopoulos

  3. Department of Pathology, Faculty of Medicine, University of Thessaly, School of Health Sciences, Biopolis, Greece

    M Ioannou

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Correspondence to M Speletas.

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Argentou, N., Vassilopoulos, G., Ioannou, M. et al. Rapid detection of MYD88-L265P mutation by PCR-RFLP in B-cell lymphoproliferative disorders. Leukemia 28, 447–449 (2014). https://doi.org/10.1038/leu.2013.294

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