Prevalence and clinical significance of the MYD88 (L265P) somatic mutation in Waldenstrom's macroglobulinemia and related lymphoid neoplasms.
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.
Department of Hematology Oncology, Fondazione IRCCS Policlinico San Matteo, 27100 Pavia, Italy. m.varettoni@smatteo.pv.it
Marzia
M
Varettoni
Luca
L
Arcaini
Silvia
S
Zibellini
Emanuela
E
Boveri
Sara
S
Rattotti
Roberta
R
Riboni
Alessandro
A
Corso
Ester
E
Orlandi
Maurizio
M
Bonfichi
Manuel
M
Gotti
Cristiana
C
Pascutto
Silvia
S
Mangiacavalli
Giorgio
G
Croci
Valeria
V
Fiaccadori
Lucia
L
Morello
Maria Luisa
ML
Guerrera
Marco
M
Paulli
Mario
M
Cazzola
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D019943:Amino Acid Substitution / Q000235:genetics / Q000502:physiology; D016022:Case-Control Studies; D005260:Female; D006801:Humans; D007075:Immunoglobulin M / Q000235:genetics; D007930:Leucine / Q000235:genetics; D008223:Lymphoma / Q000453:epidemiology / Q000209:etiology / Q000235:genetics*; D008232:Lymphoproliferative Disorders / Q000453:epidemiology / Q000209:etiology / Q000235:genetics; D008297:Male; D008875:Middle Aged; D008998:Monoclonal Gammopathy of Undetermined Significance / Q000453:epidemiology / Q000235:genetics; D020125:Mutation, Missense / Q000502:physiology; D053594:Myeloid Differentiation Factor 88 / Q000235:genetics*; D015995:Prevalence; D011392:Proline / Q000235:genetics; D008258:Waldenstrom Macroglobulinemia / Q000150:complications / Q000453:epidemiology / Q000235:genetics*
D007075:Immunoglobulin M; C507779:MYD88 protein, human; D053594:Myeloid Differentiation Factor 88; D011392:Proline; D007930:Leucine