Origin of Waldenstrom's macroglobulinaemia Ram  on García-Sanz a, * , Cristina Jim  enez a , Noemí Puig a , Bruno Paiva b , Norma C. Guti  errez a , Paula Rodríguez-Otero b , Julia Almeida c , Jesús San Miguel b , Alberto Orf ~ ao c , Marcos Gonz  alez a , Martín P  erez-Andr  es c a Servicio de Hematología, Hospital Universitario de Salamanca, Instituto de Investigaci on Biom edica de Salamanca, Centro de Investigaci on del C ancer de Salamanca, Salamanca, Spain b Clínica Universidad de Navarra, Centro de Investigaci on M edica Aplicada, Instituto De Investigaci on Sanitaria De Navarra, Pamplona, Spain c Servicio General de Citometría de la Universidad de Salamanca, Salamanca, Spain Keywords: Waldenstrom's macroglobulinaemia Flow cytometry Immunophenotyping B lymphocytes abstract Waldenstrom's macroglobulinaemia (WM) is an MYD88 L265P - 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 þ /CD22 lowþ / CD23 e /CD25 þ /CD27 þ /CD45 þ /CD38 lowþ /SmIgM þ (negative for CD5, CD10, CD11c, CD103). This immunophenotype matches memory B cells (smIgM e/þ /CD10 e /CD19 þ /CD20 þ /CD27 þ /CD38 lowþ /CD45 þ ), representing 30% of B cells in the blood. Fifty percent of them have not undergone class switch recombination and are IgM þ . 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. How- ever, some WM cells are CD27  , MYD88 WT , 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. © 2016 Elsevier Ltd. All rights reserved. * Corresponding author. Servicio de Hematología, Hospital Universitario de Salamanca, Pº San Vicente 58-182, 37007 Sala- manca, Spain. Fax: þ34 923 29 46 24. E-mail address: rgarcias@usal.es (R. García-Sanz). Contents lists available at ScienceDirect Best Practice & Research Clinical Haematology journal homepage: www.elsevier.com/locate/beha http://dx.doi.org/10.1016/j.beha.2016.08.024 1521-6926/© 2016 Elsevier Ltd. All rights reserved. Best Practice & Research Clinical Haematology 29 (2016) 136e147 Downloaded from ClinicalKey.com at University of Pittsburgh January 31, 2017. For personal use only. No other uses without permission. Copyright ©2017. Elsevier Inc. All rights reserved.