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We performed  IGH  clonotypic sequence analysis in WM in order to determine whether a preferential  IGH  gene rearrangement was observed and to assess  IGHV  mutational status in blood and/or bone marrow samples from 36 WM patients. In addition we investigated the presence of  MYD88  L265P somatic mutation. After  IGH  VDJ locus amplification, monoclonal VDJ rearranged fragments were sequenced and analyzed.  MYD88  L265P mutation was detected by AS-PCR. The most frequent family usage was  IGHV3  (74%);  IGHV3-23  and  IGHV3-74  segments were used in 26% and 17%, respectively. Somatic hypermutation was seen in 91% of cases.  MYD88  L265P mutation was found in 65,5% of patients and absent in the 3 unmutated. These findings did not correlate with clinical findings and outcome. Conclusion.  IGH genes'  repertoire differed in WM from those observed in other B-cell disorders with a recurrent  IGHV3-23  and  IGHV3-74  usage; monoclonal  IGHV  was mutated in most cases, and a high but not omnipresent prevalence of  MYD88  L265P mutation was observed. In addition, the identification of 3 patients with unmutated  IGHV  gene segments, negative for the  MYD88  L265P mutation, could support the hypothesis that an extra-germinal B-cell may represent the originating malignant cell in this minority of WM patients.

biomed research international

Clonotypic Analysis of Immunoglobulin Heavy Chain Sequences in Patients with Waldenström’s Macroglobulinemia: Correlation with<i>MYD88</i>L265P Somatic Mutation Status, Clinical Features, and Outcome

Clonotypic Analysis of Immunoglobulin Heavy Chain Sequences in Patients with Waldenström’s Macroglobulinemia: Correlation withMYD88L265P Somatic Mutation Status, Clinical Features, and Outcome