Prevalence and clinical significance of the MYD88 (L265P) somatic mutation in Waldenstrom's macroglobulinemia and related lymphoid neoplasms.

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Abstract

A study has shown that MYD88 (L265P) is a recurring somatic mutation in Waldenström's macroglobulinemia (WM). We developed an allele-specific polymerase chain reaction (PCR) for this mutation, and analyzed bone marrow or peripheral blood samples from 58 patients with WM, 77 with IgM monoclonal gammopathy of undetermined significance (IgM-MGUS), 84 with splenic marginal zone lymphoma (SMZL), and 52 with B-cell chronic lymphoproliferative disorders (B-CLPD). MYD88 (L265P) was detected in 58/58 (100%) patients with WM, 36/77 (47%) with IgM-MGUS, 5/84 (6%) with SMZL, and 3/52 (4%) with B-CLPD. Compared to IgM-MGUS patients with wild-type MYD88, those carrying MYD88 (L265P) showed significantly higher levels of IgM (P <.0001) and presented Bence-Jones proteinuria more frequently at diagnosis (P = .002). During follow-up, 9 patients with IgM-MGUS progressed to WM or to marginal zone lymphoma. Using a case-control approach, the risk of evolution of patients carrying MYD88 (L265P) was significantly higher than that of patients with wild-type MYD88 (odds ratio 4.7, 95% confidence interval 0.8 to 48.7, P = .047). These findings indicate that the allele-specific PCR we developed is a useful diagnostic tool for patients with WM or IgM-MGUS. In this latter condition, MYD88 (L265P) is associated with greater disease burden and higher risk of disease progression, and the mutation may therefore also represent a useful prognostic marker.

Original languageEnglish
Pages (from-to)2522-2528
Number of pages7
JournalBlood
Volume121
Issue number13
DOIs
Publication statusPublished - Mar 28 2013

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Waldenstrom Macroglobulinemia
Monoclonal Gammopathy of Undetermined Significance
Immunoglobulin M
Mutation
Neoplasms
Polymerase chain reaction
Lymphoma
Lymphoproliferative Disorders
B-Lymphocytes
Alleles
Polymerase Chain Reaction
Proteinuria
Bone
Blood
Disease Progression
Cells
Bone Marrow
Odds Ratio
Confidence Intervals

ASJC Scopus subject areas

  • Hematology
  • Biochemistry
  • Cell Biology
  • Immunology

Cite this

@article{9eefbce9ec1c48f1b11659f31b7a8639,
title = "Prevalence and clinical significance of the MYD88 (L265P) somatic mutation in Waldenstrom's macroglobulinemia and related lymphoid neoplasms.",
abstract = "A study has shown that MYD88 (L265P) is a recurring somatic mutation in Waldenstr{\"o}m's macroglobulinemia (WM). We developed an allele-specific polymerase chain reaction (PCR) for this mutation, and analyzed bone marrow or peripheral blood samples from 58 patients with WM, 77 with IgM monoclonal gammopathy of undetermined significance (IgM-MGUS), 84 with splenic marginal zone lymphoma (SMZL), and 52 with B-cell chronic lymphoproliferative disorders (B-CLPD). MYD88 (L265P) was detected in 58/58 (100{\%}) patients with WM, 36/77 (47{\%}) with IgM-MGUS, 5/84 (6{\%}) with SMZL, and 3/52 (4{\%}) with B-CLPD. Compared to IgM-MGUS patients with wild-type MYD88, those carrying MYD88 (L265P) showed significantly higher levels of IgM (P <.0001) and presented Bence-Jones proteinuria more frequently at diagnosis (P = .002). During follow-up, 9 patients with IgM-MGUS progressed to WM or to marginal zone lymphoma. Using a case-control approach, the risk of evolution of patients carrying MYD88 (L265P) was significantly higher than that of patients with wild-type MYD88 (odds ratio 4.7, 95{\%} confidence interval 0.8 to 48.7, P = .047). These findings indicate that the allele-specific PCR we developed is a useful diagnostic tool for patients with WM or IgM-MGUS. In this latter condition, MYD88 (L265P) is associated with greater disease burden and higher risk of disease progression, and the mutation may therefore also represent a useful prognostic marker.",
author = "Marzia Varettoni and Luca Arcaini and Silvia Zibellini and Emanuela Boveri and Sara Rattotti and Roberta Riboni and Alessandro Corso and Ester Orlandi and Maurizio Bonfichi and Manuel Gotti and Cristiana Pascutto and Silvia Mangiacavalli and Giorgio Croci and Valeria Fiaccadori and Lucia Morello and Guerrera, {Maria Luisa} and Marco Paulli and Mario Cazzola",
year = "2013",
month = "3",
day = "28",
doi = "10.1182/blood-2012-09-457101",
language = "English",
volume = "121",
pages = "2522--2528",
journal = "Blood",
issn = "0006-4971",
publisher = "American Society of Hematology",
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TY - JOUR

T1 - Prevalence and clinical significance of the MYD88 (L265P) somatic mutation in Waldenstrom's macroglobulinemia and related lymphoid neoplasms.

AU - Varettoni, Marzia

AU - Arcaini, Luca

AU - Zibellini, Silvia

AU - Boveri, Emanuela

AU - Rattotti, Sara

AU - Riboni, Roberta

AU - Corso, Alessandro

AU - Orlandi, Ester

AU - Bonfichi, Maurizio

AU - Gotti, Manuel

AU - Pascutto, Cristiana

AU - Mangiacavalli, Silvia

AU - Croci, Giorgio

AU - Fiaccadori, Valeria

AU - Morello, Lucia

AU - Guerrera, Maria Luisa

AU - Paulli, Marco

AU - Cazzola, Mario

PY - 2013/3/28

Y1 - 2013/3/28

N2 - A study has shown that MYD88 (L265P) is a recurring somatic mutation in Waldenström's macroglobulinemia (WM). We developed an allele-specific polymerase chain reaction (PCR) for this mutation, and analyzed bone marrow or peripheral blood samples from 58 patients with WM, 77 with IgM monoclonal gammopathy of undetermined significance (IgM-MGUS), 84 with splenic marginal zone lymphoma (SMZL), and 52 with B-cell chronic lymphoproliferative disorders (B-CLPD). MYD88 (L265P) was detected in 58/58 (100%) patients with WM, 36/77 (47%) with IgM-MGUS, 5/84 (6%) with SMZL, and 3/52 (4%) with B-CLPD. Compared to IgM-MGUS patients with wild-type MYD88, those carrying MYD88 (L265P) showed significantly higher levels of IgM (P <.0001) and presented Bence-Jones proteinuria more frequently at diagnosis (P = .002). During follow-up, 9 patients with IgM-MGUS progressed to WM or to marginal zone lymphoma. Using a case-control approach, the risk of evolution of patients carrying MYD88 (L265P) was significantly higher than that of patients with wild-type MYD88 (odds ratio 4.7, 95% confidence interval 0.8 to 48.7, P = .047). These findings indicate that the allele-specific PCR we developed is a useful diagnostic tool for patients with WM or IgM-MGUS. In this latter condition, MYD88 (L265P) is associated with greater disease burden and higher risk of disease progression, and the mutation may therefore also represent a useful prognostic marker.

AB - A study has shown that MYD88 (L265P) is a recurring somatic mutation in Waldenström's macroglobulinemia (WM). We developed an allele-specific polymerase chain reaction (PCR) for this mutation, and analyzed bone marrow or peripheral blood samples from 58 patients with WM, 77 with IgM monoclonal gammopathy of undetermined significance (IgM-MGUS), 84 with splenic marginal zone lymphoma (SMZL), and 52 with B-cell chronic lymphoproliferative disorders (B-CLPD). MYD88 (L265P) was detected in 58/58 (100%) patients with WM, 36/77 (47%) with IgM-MGUS, 5/84 (6%) with SMZL, and 3/52 (4%) with B-CLPD. Compared to IgM-MGUS patients with wild-type MYD88, those carrying MYD88 (L265P) showed significantly higher levels of IgM (P <.0001) and presented Bence-Jones proteinuria more frequently at diagnosis (P = .002). During follow-up, 9 patients with IgM-MGUS progressed to WM or to marginal zone lymphoma. Using a case-control approach, the risk of evolution of patients carrying MYD88 (L265P) was significantly higher than that of patients with wild-type MYD88 (odds ratio 4.7, 95% confidence interval 0.8 to 48.7, P = .047). These findings indicate that the allele-specific PCR we developed is a useful diagnostic tool for patients with WM or IgM-MGUS. In this latter condition, MYD88 (L265P) is associated with greater disease burden and higher risk of disease progression, and the mutation may therefore also represent a useful prognostic marker.

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U2 - 10.1182/blood-2012-09-457101

DO - 10.1182/blood-2012-09-457101

M3 - Article

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AN - SCOPUS:84878423649

VL - 121

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EP - 2528

JO - Blood

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SN - 0006-4971

IS - 13

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