Waldenström's macroglobulinemia: Two malignant clones in a monoclonal disease? Molecular background and clinical reflection

Eur J Haematol. 2017 Dec;99(6):469-478. doi: 10.1111/ejh.12959. Epub 2017 Oct 10.


Waldenström's macroglobulinemia (WM) is a complex disease characterized by apparent morphological heterogeneity within the malignant clonal cells representing a continuum of small lymphocytes, plasmacytoid lymphocytes, and plasma cells. At the molecular level, the neoplastic B cell-derived clone has undergone somatic hypermutation, but not isotype switching, and retains the capability of plasmacytic differentiation. Although by classical definition, WM is formed by monoclonal expansion, long-lived clonal B lymphocytes are of heterogeneous origin. Even more, according to current opinion, plasma cells also conform certain population with pathogenic and clinical significance. In this article, we review the recent advances in the WM clonal architecture, briefly describe B-cell development during which the molecular changes lead to the malignant transformation and mainly focus on differences between two principal B-lineage clones, including analysis of their genome and transcriptome profiles, as well as immunophenotype features. We assume that the correct identification of a number of specific immunophenotypic molecular and expression alterations leading to proper aberrant clone detection can help to guide patient monitoring throughout treatment and successfully implement therapy strategies directed against both B- and plasma cell tumor WM clones.

Keywords: B-Lymphocytes; Clone Cells; Immunophenotyping; Waldenstrom Macroglobulinemia.

Publication types

  • Review

MeSH terms

  • Animals
  • B-Lymphocytes / metabolism
  • B-Lymphocytes / pathology
  • Clonal Evolution / genetics
  • Gene Expression Regulation, Neoplastic
  • Genetic Heterogeneity
  • Genetic Variation
  • Humans
  • Immunophenotyping
  • Phenotype
  • Plasma Cells / metabolism
  • Plasma Cells / pathology
  • Signal Transduction
  • Tumor Burden
  • Waldenstrom Macroglobulinemia / diagnosis*
  • Waldenstrom Macroglobulinemia / etiology*