Origin of Waldenstrom's macroglobulinaemia.
Waldenstrom's macroglobulinaemia (WM) is an MYD88L265P-mutated lymphoplasmacytic lymphoma that invades bone marrow and secretes monoclonal immunoglobulin M (IgM). WM cells are usually unable to undergo class switch recombination, and have mutated IGHV, with a typical immunophenotype CD19+/CD22low+/CD23-/CD25+/CD27+/CD45+/CD38low+/SmIgM+(negative for CD5, CD10, CD11c, CD103). This immunophenotype matches memory B cells (smIgM-/+/CD10-/CD19+/CD20+/CD27+/CD38low+/CD45+), representing 30% of B cells in the blood. Fifty percent of them have not undergone class switch recombination and are IgM+. These cells have suffered somatic hypermutation as WM cells. Genetic abnormalities do not abrogate the capacity to progress to plasma cells that usually belong to the clonal WM compartment, with a normal immunophenotype and functional characteristics. However, some WM cells are CD27-, MYD88WT, without somatic hypermutation, or with class switch recombination capable of reactivation. Thus, most data support a B-memory-cell origin for WM, but a small fraction of cases may have a different origin.
Servicio de Hematología, Hospital Universitario de Salamanca, Instituto de Investigación Biomédica de Salamanca, Centro de Investigación del Cáncer de Salamanca, Salamanca, Spain. Electronic address: rgarcias@usal.es.
Ramón
R
García-Sanz
Servicio de Hematología, Hospital Universitario de Salamanca, Instituto de Investigación Biomédica de Salamanca, Centro de Investigación del Cáncer de Salamanca, Salamanca, Spain.
Cristina
C
Jiménez
Servicio de Hematología, Hospital Universitario de Salamanca, Instituto de Investigación Biomédica de Salamanca, Centro de Investigación del Cáncer de Salamanca, Salamanca, Spain.
Noemí
N
Puig
Clínica Universidad de Navarra, Centro de Investigación Médica Aplicada, Instituto De Investigación Sanitaria De Navarra, Pamplona, Spain.
Bruno
B
Paiva
Servicio de Hematología, Hospital Universitario de Salamanca, Instituto de Investigación Biomédica de Salamanca, Centro de Investigación del Cáncer de Salamanca, Salamanca, Spain.
Norma C
NC
Gutiérrez
Clínica Universidad de Navarra, Centro de Investigación Médica Aplicada, Instituto De Investigación Sanitaria De Navarra, Pamplona, Spain.
Paula
P
Rodríguez-Otero
Servicio General de Citometría de la Universidad de Salamanca, Salamanca, Spain.
Julia
J
Almeida
Clínica Universidad de Navarra, Centro de Investigación Médica Aplicada, Instituto De Investigación Sanitaria De Navarra, Pamplona, Spain.
Jesús
J
San Miguel
Servicio General de Citometría de la Universidad de Salamanca, Salamanca, Spain.
Alberto
A
Orfão
Servicio de Hematología, Hospital Universitario de Salamanca, Instituto de Investigación Biomédica de Salamanca, Centro de Investigación del Cáncer de Salamanca, Salamanca, Spain.
Marcos
M
González
Servicio General de Citometría de la Universidad de Salamanca, Salamanca, Spain.
Martín
M
Pérez-Andrés
D019943:Amino Acid Substitution; D015703:Antigens, CD / Q000235:genetics / Q000276:immunology; D006801:Humans; D007075:Immunoglobulin M / Q000235:genetics / Q000276:immunology; D007156:Immunologic Memory / Q000235:genetics*; D020125:Mutation, Missense; D053594:Myeloid Differentiation Factor 88 / Q000235:genetics / Q000276:immunology; D010950:Plasma Cells / Q000276:immunology*; D027041:Somatic Hypermutation, Immunoglobulin / Q000235:genetics*; D008258:Waldenstrom Macroglobulinemia / Q000235:genetics / Q000276:immunology
D015703:Antigens, CD; D007075:Immunoglobulin M; C507779:MYD88 protein, human; D053594:Myeloid Differentiation Factor 88
B lymphocytes; Flow cytometry; Immunophenotyping; Waldenstrom's macroglobulinaemia